Pregnane X Receptor Compositions, Crystals and Uses Thereof

ABSTRACT

The present invention relates, inter alia, to PXR polypeptides and crystals that are useful, for example, for crystallization and in assays for identification of modulators of PXR.

This application claims the benefit of U.S. provisional patent application No. 60/718,516; filed Sep. 19, 2005, which is herein incorporated by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates, inter alia, to pregane X receptor (PXR) polypeptides, polynucleotides, crystals, methods of use thereof and assays for identifying PXR modulators.

BACKGROUND OF THE INVENTION

Two major problems associated with the administration of drugs have been poor pharmacokinetics (PK) and undesired drug-drug interactions. It is known that the cytochrome P450 (CYP) 3A family of enzymes are important in human drug metabolism because they metabolize the majority of commercially available drugs (Wrighton et al., Drug metabolism reviews 32: 339-361 (2000)). In 1998, the pregnane X receptor (PXR), which orchestrates the induction of some of the major genes involved in drug detoxification, was identified. (Lehmann, et al., J. Clin. Invest. 102(5):1016-1023 (1998); Genbank Accession No. AF061056). PXR, also known as steroid and xenobiotic receptor (SXR or PAR), was shown to be activated by many drugs, steroids such as pregnenolone 16α-carbonitrile; RU-486; dexamethasone; and rifampicin (Kliewer et al., Cell 92(1):73-82 (1998); Kliewer et al., J. Lipid Res. 43:359-364 (2002)) and St. John's wort (hyperforin) (Moore et al., Proc. Natl. Acad. Sci. USA; 97(13):7500-7502 (2000)) and recently was shown to be a sensor for bile acids (Staudinger et al., Drug Metab. Dispos. 29(11):1467-1472 (2001); Staudinger et al., Proc. Natl. Acad. Sci. USA. 98(6):3369-74 (2001)). PXR is also activated by other drugs such as clotrimazole (Lehmann et al., J. Clin. Invest. 102:1016-1023 (1998)); 11β-hydroxylase inhibitor metyrapone (Goodwin et al., Mol. Pharmacol. 56:1329-1339 (1999); Wright et al., Biochem. Soc. Trans. 27:387-391 (1998)); troglitazone (Jones et al, Mol. Endocrinol. 14:27-39 (2000)); ritonavir (Dussault et al., J. Biol. Chem. 276:33309-33312 (2001)) and taxol (Synold et al., Nat. Med. 7:584-590 (2001)) as well as by environmental pollutants such as bisphenol A, diethylhexylphthalate, and nonylphenol (Masuyama et al., Mol. Endocrinol. 14:421-428 (2000); Takeshita et al., Eur. J. Endocrinol. 145:513-517 (2001)). PXR plays a key role in the regulation of both drug metabolism and efflux by modulating a plethora of genes encoding cytochrome P450 enzymes (CYPs, especially CYP3A4) and a multidrug resistant gene ABCB1 (Synold et al., Nat. Med. 7(5):584-590 (2001)). Together, these proteins are responsible for the elimination of >50% of all drugs. Identification of candidate pharmaceutical treatments which interact with PXR and are likely to be metabolized by the PXR system is enormously useful information when performing an early evaluation of the safety and pharmacokinetic profile of the treatment. Therefore, high-throughput screening assays detecting PXR-mediated induction have become pivotal at early discovery stages in order to decrease the time line for clinical drug development. Moreover, crystals of PXR are useful for these purposes in that they provide a greater understanding of ligand interactions with the protein and allow computer-assisted, structure-based evaluation of candidate treatments.

Several crystals comprising PXR are known in the art. For example, the structure of apo-PXR-LBD crystal comprising space group P4₃2₁2 was solved with a 2.52 Å resolution (Watkins et al., Science 292:2329-2333 (2001)); the structure of PXR-LBD/SR12813 crystal comprising space group P4₃2₁2 was solved with a 2.76 Å resolution (Watkins et al., Science 292:2329-2333 (2001)); the structure of PXR-LBD/Hyperforin comprising space group P4₃2₁2 was solved with a 2.15 Å resolution (Watkins et al., Biochemistry 42:1430-1438 (2003)).

In addition, the structure of PXR-LBD/SR12813/SRC1 crystal comprising space group P2₁2₁2₁ was solved with a resolution of 2.00 Å (Watkins et al., J. Mol. Biol. 331:815-828 (2003)). The crystal in Watkins et al., however, comprised PXR-LBD complexed with SRC1 and not covalently bound in a hybrid.

SUMMARY OF THE INVENTION

The present invention provides a polypeptide and crystalline composition comprising a highly advantageous hybrid construct wherein PXR or PXR-LBD (PXR ligand binding domain) is tethered to SRC1 peptide. SRC1 is a coactivator which binds to and stabilizes PXR (see e.g., Watkins, et al.). The solubility of PXR or PXR-LBD is also increased by binding to SRC1. Tethering SRC1 to PXR or PXR-LBD allows PXR to be saturated, with SRC1, to a greater level that when the two polypeptides are merely complexed. This highly-saturated level of binding to SRC1 results in a highly soluble and highly stabilized PXR or PXR-LBD. Moreover, saturation of PXR-LBD with SRC1 peptide is convenient, aids in the generation of high quality crystalline complexes and aids in the generation of high quality binding data (e.g., temperature dependent circular dichroism data) between the hybrid and a candidate binding compound. In an embodiment, the binding of PXR-LBD and SRC1 peptide is optimized in a hybrid of the invention by placing a 10 amino acid peptide linker between the PXR-LBD and the SRC1 peptide.

The present invention provides an isolated fusion polypeptide comprising pregnane X receptor (PXR) polypeptide or a fragment thereof, optionally fused to a linker polypeptide, fused to SRC-1 polypeptide or a fragment thereof. In an embodiment of the invention, the linker comprises from about 8 to about 13 amino acids. In an embodiment of the invention, the PXR fragment is the ligand binding domain (LBD) of pregnane X receptor. In an embodiment of the invention, the pregnane X receptor polypeptide or fragment thereof comprises the amino acid sequence set forth in SEQ ID NO: 1 or 2. In an embodiment of the invention, the SRC-1 polypeptide or fragment thereof comprises the amino acid sequence set forth in SEQ ID NO: 3 or SLTERHKILHRLLQEGSPS (SEQ ID NO: 35). In an embodiment of the invention, the fusion polypeptide is complexed to a member selected from the group consisting of SR12813, hyperforin, clotrimazole, ritonavir, sulfopyrole, pregnane-16α-carbonitrile, RU-486, rifampicin, dexamethasone, paclitaxel, metyrapone, bisphenol A, diethylhexylphthalate, nonylphenol, phthalate, cisplatin, chenodeoxycholic acid, deoxycholic acid, lithocholic acid, 17β-estradiol (estradiol), pregnenolone (5-pregneno-3β-ol-20-one), progesterone, and Medroxyprogesterone-acetate (MPA).

The present invention provides a composition comprising PXR polypeptide or a fragment thereof and SRC-1 polypeptide or a fragment thereof. In an embodiment of the invention, the pregnane X receptor polypeptide or fragment thereof comprises the amino acid sequence set forth in SEQ ID NO: 1 or 2. In an embodiment of the invention, the SRC-1 polypeptide or fragment thereof comprises the amino acid sequence set forth in SEQ ID NO: 3 or SLTERHKILHRLLQEGSPS (SEQ ID NO: 35).

The present invention provides, an isolated polynucleotide encoding the fusion polypeptide of claim 1. In an embodiment of the invention, the polynucleotide comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 22, 24, 26, 28, 30 and 32. The present invention also provides a recombinant vector comprising said polynucleotide. The present invention further provides an isolated host cell comprising said vector.

The present invention provides an isolated polynucleotide comprising a bicistronic cassette comprising a polynucleotide encoding pregnane X receptor or a fragment thereof, which is adjacent to a ribosome binding site, which is adjacent to a polynucleotide encoding SRC-1 or a fragment thereof. In an embodiment of the invention, the polynucleotide encoding the pregnane X receptor is located 5′ of the ribosome binding site. In an embodiment of the invention, the polynucleotide encoding SRC-1 or said fragment thereof is located 5′ of the ribosome binding site. In an embodiment of the invention, the polynucleotide is operably linked to a promoter. The present invention also provides a recombinant vector comprising the polynucleotide comprising the cassette. An isolated host cell comprising the vector also forms part of the present invention.

The present invention also provides a crystalline composition comprising a hybrid polypeptide comprising PXR polypeptide or a ligand binding domain (LBD) thereof tethered, optionally by a peptide linker, to SRC-1 polypeptide or a fragment thereof, optionally complexed with SR12813. In an embodiment of the invention, the crystal comprises a dimer which comprises two monomers comprising said hybrid polypeptides. In an embodiment of the invention, the crystal comprises a tetragonal space group whose asymmetric unit comprises one monomer or orthorhombic space group whose asymmetric unit comprising two monomers. In an embodiment of the invention, the crystal comprises a hybrid polypeptide comprising PXR polypeptide or a ligand binding domain (LBD) thereof tethered by a peptide linker to SRC-1 polypeptide or a fragment thereof, optionally complexed with SR12813 or a structural homologue thereof, wherein the polypeptide three dimensional structure is characterized by structural coordinates comprising a root mean square deviation of conserved or common residue backbone atoms (e.g., backbone atoms of residues common to both structures being compared) or alpha carbon atoms of less than about 1.5 Å when superimposed on backbone atoms or alpha carbon atoms described by structural coordinates of Table 3a, 3b, 4a, 5a or 5b; and wherein the three dimensional coordinates of the SR12813 or the structural homologue thereof are characterized by structural coordinates comprising a root mean square deviation of backbone atoms or alpha carbon atoms over those residues commonly present in the compared structures of less than about 1.5 Å (e.g., about 1 Å, about 0.75 Å, about 0.5 Å, about 0.25 Å or about 0.1 Å) when superimposed on atoms described by structural coordinates of Table 5c. In an embodiment of the invention, the PXR polypeptide or ligand binding domain thereof comprises the amino acid sequence set forth in SEQ ID NO: 1 or 2. In an embodiment of the invention, the SRC-1 polypeptide or said fragment thereof comprises the amino acid sequence set forth in SEQ ID NO: 3 or SLTERHKILHRLLQEGSPS (SEQ ID NO: 35). In an embodiment of the invention, solvent molecules are associated with the crystalline polypeptide. In an embodiment of the invention, the three dimensional structure of the solvent molecules are characterized by the coordinates set forth in Table 3c or Table 5d. In an embodiment of the invention, the crystal comprises a crystal lattice in a space group selected from the group consisting of P2₁2₁2₁ and P4₃2₁2. In an embodiment of the invention, the crystal comprises a unit cell with dimensions selected from the group consisting of a=84.2 Å, b=90.0 Å, c=106.6 Å, α=β=γ=90°; a=b=94.2 Å, c=88.2 Å, α=β=γ=90°; and a=86.0 Å, b=89.3 Å, c=106.0 Å, α=β=γ=90°. The present invention provides a crystalline composition comprising a dimer which comprises one or more monomers comprising a polypeptide comprising the amino acid sequence of SEQ ID NO: 24, which is optionally complexed with SR12813 wherein: (a) a first monomer is characterized by the structural coordinates set forth in Table 3a and a second monomer is characterized by the structural coordinates set forth in Table 3b; (b) a monomer is characterized by the structural coordinates set forth in Table 4a; or (c) a first monomer is characterized by the structural coordinates set forth in Table 5a, a second monomer is characterized by the structural coordinates set forth in Table 5b; and SR12813 complexed with said polypeptides is characterized by the structural coordinates set forth in Table 5c.

The present invention provides a method for stabilizing a pregnane X receptor polypeptide or fragment thereof comprising providing said polypeptide or fragment in association with SRC-1 or a fragment thereof. The present invention also provides a method for stabilizing a pregnane X receptor polypeptide or fragment thereof comprising tethering said polypeptide or fragment to SRC-1 or a fragment thereof. In an embodiment of the invention, said pregnane X receptor or fragment thereof is tethered to SRC-1 or the fragment thereof by a linker.

The present invention also provides a method for identifying a modulator of PXR, a modulator of CYP3A4 activation or a modulator of in vivo drug half-life comprising: (a) contacting a composition comprising PXR or a fragment or fusion thereof and SRC-1 or a fragment of fusion thereof with a substance to be tested for the presence of the modulator; and (b) determining the ellipticity of the composition contacted with the substance; whereby the substance is selected if the ellipticity of the composition alone is different from the ellipticity of the composition that is in contact with the substance.

The present invention also provides a method for identifying a modulator of PXR, a modulator of CYP3A4 activation or a modulator of in vivo drug half-life comprising: (1) contacting a composition comprising PXR or a fragment or fusion thereof and SRC-1 or a fragment of fusion thereof with a substance to be tested for the presence of a modulator; and (2) determining if the substance binds to said PXR or fragment or fusion thereof; whereby the substance is selected if binding is observed.

The present invention also provides a method for identifying a modulator of PXR, a modulator of CYP3A4 activation or a modulator of in vivo drug half-life comprising: (A) contacting an isolated host cell comprising PXR or a fragment or fusion and SRC-1 or a fragment or fusion thereof and a reporter gene operably linked to a CYP3A4 promoter or to an ABCB1 promoter with a substance to be tested for the presence of the modulator; and (B) determining if the reporter gene is expressed; whereby the substance is selected if the reporter gene, in the cell contacted with said substance, is expressed at a higher or lower level than a reporter gene in a host cell that is not contacted with said substance.

The present invention also provides a method for identifying a modulator of PXR, a modulator of CYP3A4 activation or a modulator of in vivo drug half-life comprising: (i) contacting a composition comprising PXR or a fragment or fusion thereof and SRC-1 or a fragment of fusion thereof with a ligand that is known to bind PXR or said fragment or fusion thereof and with a substance to be tested for the presence of a modulator or binder; and (ii) determining if the substance being tested reduces binding of the ligand to PXR or the fragment or fusion thereof; whereby the substance is selected if binding of the ligand to PXR or the fragmentor fusion thereof, in the presence of the substance, is less than binding of the ligand to PXR or the fragment or fusion thereof in the absence of the substance.

The present invention also provides a method for determining whether the half-life of a drug will be affected by the cytochome P450 pathway when administered to a subject in vivo, comprising (i) contacting an in vitro composition comprising PXR or a fragment or fusion thereof and SRC-1 or a fragment of fusion thereof with the drug; and (ii) determining whether the drug binds to PXR or the fragment or fusion thereof or modulates PXR or the fragment or fusion thereof; whereby the half-life of the drug is determined to be affected by the P450 pathway, when administered in vivo, if said binding or modulation is observed.

The present invention also provides a method for determining whether a first drug will affect the half-life of a second drug when co-administered to a subject in vivo comprising: (i) contacting an in vitro composition comprising PXR or a fragment or fusion thereof and SRC-1 or a fragment of fusion thereof with said first drug; and (ii) determining whether said first drug binds to or modulates PXR; whereby the half-life of the second drug is determined to be affected by in vivo co-administration with the first drug if said binding or modulation is observed.

The present invention also provides a method for determining whether a drug will be metabolized, when administered to a subject in vivo, into a prodrug comprising (i) contacting an in vitro composition comprising PXR or a fragment or fusion thereof and SRC-1 or a fragment of fusion thereof with the drug; and (ii) determining whether the drug binds to or modulates PXR; whereby it is determined that the drug will be metabolized into a prodrug, when administered in vivo, if said binding or modulation is observed.

The present invention also provides a method for identifying a PXR agonist or antagonist comprising the steps of: a) crystallizing PXR or a fragment thereof fused to SRC-1 or a fragment thereof to form at least one crystal; b) irradiating the crystal produced by step (a) to obtain a diffraction pattern of said crystal; c) determining the atomic coordinates of the three-dimensional structure of the PXR or the fragment or fusion thereof from the diffraction pattern; d) using the atomic coordinates and one or more molecular modeling techniques to identify an agent that interacts with the PXR; and e) determining if the agonist or antagonist increases or decreases the in vivo activation of cytochrome P450 enzymes or the multidrug resistant gene ABCB1, binds to or modulates PXR or modulates half life of drugs in vivo; wherein the agonist or antagonist is selected if it increases or decreases the in vivo activation of cytochrome P450 enzymes or the multidrug resistant gene ABCB1, binds to or modulates PXR or modulates half life of drugs in vivo.

DETAILED DESCRIPTION OF THE INVENTION

The nuclear xenobiotic receptor PXR is activated by a wide variety of clinically used drugs and serves as a master regulator of drug metabolism and excretion gene expression in mammals. Upon activation, PXR binds to DNA and regulates a network of genes in the liver and intestine that are involved in the metabolism and efflux of potentially harmful xenobiotics. In addition, it is also responsible for an important class of harmful drug-drug interactions. The development of high throughput ligand binding assays as well as the determination of crystal structures of PXR ligand binding domain (LBD) will help to prevent the PXR-mediated effects. Two bicistronic constructs (containing PXR-LBD and SRC-1, a fragment of human steroid receptor coactivator-1), and several tethered PXR-SRC constructs were engineered and expressed in E. coli cells. The purified proteins were suitable for ligand binding assays and/or X-ray crystallization.

In accordance with the present invention, there may be employed conventional molecular biology, microbiology, and recombinant DNA techniques within the skill of the art. Such techniques are explained fully in the literature. See, e.g., Sambrook, Fritsch & Maniatis, Molecular Cloning: A Laboratory Manual, Second Edition (1989) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (herein “Sambrook et al., 1989”); DNA Cloning: A Practical Approach, Volumes I and II (D. N. Glover ed. 1985); Oligonucleotide Synthesis (M. J. Gait ed. 1984); Nucleic Acid Hybridization [B. D. Hames & S. J. Higgins eds. (1985)]; Transcription And Translation [B. D. Hames & S. J. Higgins, eds. (1984)]; Animal Cell Culture [R. I. Freshney, ed. (1986)]; Immobilized Cells And Enzymes [IRL Press, (1986)]; B. Perbal, A Practical Guide To Molecular Cloning (1984); F. M. Ausubel et al. (eds.), Current Protocols in Molecular Biology, John Wiley & Sons, Inc. (1996) (herein “Ausubel et al., 1996”).

The term “PXR-linker-SRC-1” includes any polypeptide or encoding polynucleotide or crystal thereof comprising PXR or a fragment thereof (e.g., PXR-LBD) fused to a polypeptide linker of any size (e.g., 8, 10 or 13 amino acids), fused to SRC-1 polypeptide or a fragment thereof (e.g., SLTERHKILHRLLQEGSPS (SEQ ID NO: 35)). Coexpressing PXR or a fragment thereof (e.g., PXR-LBD or PXR_(full)) with SRC-1 or a fragment thereof (e.g., SEQ ID NO: 35) or expressing PXR or a fragment thereof (e.g., PXR-LBD) tethered to SRC-1 or a fragment thereof (e.g., tethered by a linker) stabilizes PXR. PXR or the fragment thereof (e.g., PXR-LBD) is stabilized in the sense that its solubility and activity is increased over that of PXR that is untethered or expressed without SRC-1.

The term “subject” includes any organism, such as a mammal (e.g., human, dog, cat, rat, rabbit, monkey, gorilla, chimpanzee or mouse).

The meaning of the term “PXR” or “pregnane X receptor” is well known in the art. In an embodiment of the invention, the amino acid sequence of a human PXR is (PXR-LBD (ligand binding domain) is underscored):

(SEQ ID NO: 1) MEVRPKESWNHADFVHCEDTESVPGKPSVNADEEVGGPQICRVCGDKATGYHFNVMTCEGCKGFFRRAMKRNARL RCPFRKGACEITRKTRRQCQACRLRKCLESGMKKEMIMSDEAVEERRALIKRKKSERTGTQPLGVQGLTEEQRMM IRELMDAQMKTFDTTFSHFKNFRLPGVLSSGCELPESLQAPSREEAAKWSQVRKDLCSLKVSLQLRGEDGSVWNY KPPADSGGKEIFSLLPHMADMSTYMFKGIISFAKVISYFRDLPIEDQISLLKGAAFELCQLRFNTVFNAETGTWE CGRLSYCLEDTAGGFQQLLLEPMLKFHYMLKKLQLHEEEYVLMQAISLFSPDRPGVLQHRVVDQLQEQFAITLKS YIECNRPQPAHRFLFLKIMAMLTELRSINAQHTQRLLRIQDIHPFATPLMQELFGITGS

In an embodiment, the amino acid sequence of wild-type human PXR-LBD (residue 130-434) is set forth below:

(SEQ ID NO: 2) SERTGTQPLGVQGLTEEQRMMIRELMDAQMKTFDTTFSHFKNFRLPGVLSSGCELPESLQAPSREEAAKWSQVRK DLCSLKVSLQLRGEDGSVWNYKPPADSGGKEIFSLLPHMADMSTYMFKGIISFAKVISYFRDLPIEDQISLLKGA AFELCQLRFNTVFNAETGTWECGRLSYCLEDTAGGFQQLLLEPMLKFHYMLKKLQLHEEEYVLMQAISLFSPDRP GVLQHRVVDQLQEQFAITLKSYIECNRPQPAHRFLFLKIMAMLTELRSINAQHTQRLLRIQDIHPFATPLMQELF GITGS In an embodiment of the invention, a “fragment” of PXR is PXR-LBD (e.g., amino acids about 169 to about 473 of human PXR (Acc. No. IPI00004364.1 or Q9UNW4; or amino acids about 130 to about 434 of the polypeptide under Acc. No. NP_(—)003880.3).

The meaning of the term SRC-1 is well known in the art. In an embodiment of the invention, the amino acid sequence of a human SRC-1 is:

(SEQ ID NO: 3) MSGLGDSSSD PANPDSHKRK GSPCDTLASS TEKRRREQEN KYLEELAELL SANISDIDSL SVKPDKCKIL KKTVDQIQLM KRMEQEKSTT DDDVQKSDIS SSSQGVIEKE SLGPLLLEAL DGFFFVVNCE GRIVFVSENV TSYLGYNQEE LMNTSVYSIL HVGDHAEFVK NLLPKSLVNG VPWPQEATRR NSHTFNCRML IHPPDEPGTE NQEACQRYEV MQCFTVSQPK SIQEDGEDFQ SCLICIARRL PRPPAITGVE SFMTKQDTTG KIISIDTSSL RAAGRTGWED LVRKCIYAFF QPQGREPSYA RQLFQEVMTR GTASSPSYRF ILNDGTMLSA HTKCKLCYPQ SPDMQPFIMG IHIIDREHSG LSPQDDTNSG MSIPRVNPSV NPSISPAHGV ARSSTLPPSN SNMVSTRINR QQSSDLHSSS HSNSSNSQGS FGCSPGSQIV ANVALNQGQA SSQSSNPSLN LNNSPMEGTG ISLAQFMSPR RQVTSGLATR PRMPNNSFPP NISTLSSPVG MTSSACNNNN RSYSNIPVTS LQGMNEGPNN SVGFSASSPV LRQMSSQNSP SRLNIQPAKA ESKDNKEIAS ILNEMIQSDN SSSDGKPLDS GLLHNNDRLS DGDSKYSQTS HKLVQLLTTT AEQQLRHADI DTSCKDVLSC TGTSNSASAN SSGGSCPSSH SSLTERHKIL HRLLQEGSPS DITTLSVEPD KKDSASTSVS VTGQVQGNSS IKLELDASKK KESKDHQLLR YLLDKDEKDL RSTPNLSLDD VKVKVEKKEQ MDPCNTNPTP MTKPTPEEIK LEAQSQFTAD LDQFDQLLPT LEKAAQLPGL CETDRMDGAV TSVTIKSEIL PASLQSATAR PTSRLNRLPE LELEAIDNQF GQPGTGDQIP WTNNTVTAIN QSKSEDQCIS SQLDELLCPP TTVEGRNDEK ALLEQLVSFL SGKDETELAE LDRALGIDKL VQGGGLDVLS ERFPPQQATP PLIMEERPNL YSQPYSSPSP TANLPSPFQG MVRQKPSLGT MPVQVTPPRG AFSPGMGMQP RQTLNRPPAA PNQLRLQLQQ RLQGQQQLIH QNRQAILNQF AATAPVGINM RSGMQQQITP QPPLNAQMLA QRQRELYSQQ HRQRQLIQQQ RAMLMRQQSF GNNLPPSSGL PVQMGNPRLP QGAPQQFPYP PNYGTNPGTP PASTSPFSQL AANPEASLAN RNSMVSRGMT GNIGGQFGTG INPQMQQNVF QYPGAGMVPQ GEANFAPSLS PGSSMVPMPI PPPQSSLLQQ TPPASGYQSP DMKAWQQGAI GNNNVFSQAV QNQPTPAQPG VYNNMSITVS MAGGNTNVQN MNPMMAQMQM SSLQMPGMNT VCPEQINDPA LRHTGLYCNQ LSSTDLLKTE ADGTQQVQQV QVFADVQCTV NLVGGDPYLN QPGPLGTQKP TSGPQTPQAQ QKSLLQQLLT E

The SRC-1 sequence is also disclosed under Genbank Accession Number: NP_(—)003734. In an embodiment of the invention a “fragment” of SRC-1 comprises the amino acid sequence SLTERHKILHRLLQEGSPS (SEQ ID NO: 35; amino acids 682-700 of human SRC-1) or sc SSHSSLTERHKILHRLLQEGSPS (SEQ ID NO: 38; amino acids 678-700 of human SRC-1).

Embodiments of the present invention are set forth herein comprising PXR or SRC-1 (e.g., crystals, assays, polypeptides, polynucleotides). Also included within the scope of the present invention are embodiments comprising PXR and SRC-1 variants. Accordingly, the present invention contemplates any superficial or slight modification to the amino acid or nucleotide sequences which correspond to the polypeptides of the invention. In particular, the present invention contemplates function- and sequence-conservative variants of the nucleic acids which encode the polypeptides of the invention. “Sequence-conservative variants” of a polynucleotide sequence are those in which a change of one or more nucleotides in a given codon results in no alteration in the amino acid encoded at that position. Function-conservative variants of the polypeptides of the invention are also contemplated by the present invention. “Function-conservative variants” are those in which one or more amino acid residues in a protein or enzyme have been changed without altering the overall conformation and function of the polypeptide, including, but, by no means, limited to, replacement of an amino acid with one having similar properties. Amino acids with similar properties are well known in the art. For example, polar/hydrophilic amino acids which may be interchangeable include asparagine, glutamine, serine, cysteine, threonine, lysine, arginine, histidine, aspartic acid and glutamic acid; nonpolar/hydrophobic amino acids which may be interchangeable include glycine, alanine, valine, leucine, isoleucine, proline, tyrosine, phenylalanine, tryptophan and methionine; acidic amino acids which may be interchangeable include aspartic acid and glutamic acid and basic amino acids which may be interchangeable include histidine, lysine and arginine.

The present invention includes polynucleotides encoding PXR or SRC-1 and fusions and fragments thereof as well as nucleic acids which hybridize to the polynucleotides. Preferably, the nucleic acids hybridize under low stringency conditions, more preferably under moderate stringency conditions and most preferably under high stringency conditions. A nucleic acid molecule is “hybridizable” to another nucleic acid molecule, such as a cDNA, genomic DNA, or RNA, when a single stranded form of the nucleic acid molecule can anneal to the other nucleic acid molecule under the appropriate conditions of temperature and solution ionic strength (see Sambrook, et al., supra). The conditions of temperature and ionic strength determine the “stringency” of the hybridization. Typical low stringency hybridization conditions are 55° C., 5×SSC, 0.1% SDS, 0.25% milk, and no formamide at 42° C.; or 30% formamide, 5×SSC, 0.5% SDS at 42° C. Typical, moderate stringency hybridization conditions are similar to the low stringency conditions except the hybridization is carried out in 40% formamide, with 5× or 6×SSC at 42° C. High stringency hybridization conditions are similar to low stringency conditions except the hybridization conditions are carried out in 50% formamide, 5× or 6×SSC and, optionally, at a higher temperature (e.g., higher than 42° C.: 57° C., 59° C., 60° C., 62° C., 63° C., 65° C. or 68° C.). In general, SSC is 0.15M NaCl and 0.015M Na-citrate. Hybridization requires that the two nucleic acids contain complementary sequences, although, depending on the stringency of the hybridization, mismatches between bases are possible. The appropriate stringency for hybridizing nucleic acids depends on the length of the nucleic acids and the degree of complementation, variables well known in the art. The greater the degree of similarity or homology between two nucleotide sequences, the higher the stringency under which the nucleic acids may hybridize. For hybrids of greater than 100 nucleotides in length, equations for calculating the melting temperature have been derived (see Sambrook, et al., supra, 9.50-9.51). For hybridization with shorter nucleic acids, i.e., oligonucleotides, the position of mismatches becomes more important, and the length of the oligonucleotide determines its specificity (see Sambrook, et al., supra).

Also included in the present invention are polynucleotides comprising nucleotide sequences and polypeptides comprising amino acid sequences which are at least about 70% identical, preferably at least about 80% identical, more preferably at least about 90% identical and most preferably at least about 95% identical (e.g., 95%, 96%, 97%, 98%, 99%, 100%) to the reference PXR or SRC-1 polynucleotide or polypeptide or fragment or fusion thereof when the comparison is performed by a BLAST algorithm wherein the parameters of the algorithm are selected to give the largest match between the respective sequences over the entire length of the respective reference sequences. Polypeptides comprising amino acid sequences which are at least about 70% similar, preferably at least about 80% similar, more preferably at least about 90% similar and most preferably at least about 95% similar (e.g., 95%, 96%, 97%, 98%, 99%, 100%) to the reference PXR or SRC-1 polypeptide or fragment or fusion thereof, when the comparison is performed with a BLAST algorithm wherein the parameters of the algorithm are selected to give the largest match between the respective sequences over the entire length of the respective reference sequences, are also included in the present invention. Any composition comprising a combination of SRC-1 (or SRC-1 fragment) or a sequence variant thereof and PXR (or PXR fragment) or a sequence variant thereof, fused or unfused, are part of the present invention.

Sequence identity refers to exact matches between the nucleotides or amino acids of two sequences which are being compared. Sequence similarity refers to both exact matches between the amino acids of two polypeptides which are being compared in addition to matches between nonidentical, biochemically related amino acids. Biochemically related amino acids which share similar properties and may be interchangeable are discussed above.

The following references regarding the BLAST algorithm are herein incorporated by reference: BLAST ALGORITHMS: Altschul, S. F., et al., (1990) J. Mol. Biol. 215:403-410; Gish, W., et al., (1993) Nature Genet. 3:266-272; Madden, T. L., et al., (1996) Meth. Enzymol. 266:131-141; Altschul, S. F., et al., (1997) Nucleic Acids Res. 25:3389-3402; Zhang, J., et al., (1997) Genome Res. 7:649-656; Wootton, J. C., et al., (1993) Comput. Chem. 17:149-163; Hancock, J. M., et al., (1994) Comput. Appl. Biosci. 10:67-70; ALIGNMENT SCORING SYSTEMS: Dayhoff, M. O., et al., “A model of evolutionary change in proteins.” in Atlas of Protein Sequence and Structure, (1978) vol. 5, suppl. 3. M. O. Dayhoff (ed.), pp. 345-352, Natl. Biomed. Res. Found., Washington, D.C.; Schwartz, R. M., et al., “Matrices for detecting distant relationships.” in Atlas of Protein Sequence and Structure, (1978) vol. 5, suppl. 3.” M. O. Dayhoff (ed.), pp. 353-358, Natl. Biomed. Res. Found., Washington, D.C.; Altschul, S. F., (1991) J. Mol. Biol. 219:555-565; States, D. J., et al., (1991) Methods 3:66-70; Henikoff, S., et al., (1992) Proc. Natl. Acad. Sci. USA 89:10915-10919; Altschul, S. F., et al., (1993) J. Mol. Evol. 36:290-300; ALIGNMENT STATISTICS: Karlin, S., et al., (1990) Proc. Natl. Acad. Sci. USA 87:2264-2268; Karlin, S., et al., (1993) Proc. Natl. Acad. Sci. USA 90:5873-5877; Dembo, A., et al., (1994) Ann. Prob. 22:2022-2039; and Altschul, S. F. “Evaluating the statistical significance of multiple distinct local alignments.” in Theoretical and Computational Methods in Genome Research (S. Suhai, ed.), (1997) pp. 1-14, Plenum, New York.

Included within the scope of the invention is any embodiment set forth herein comprising a variant of a PXR or SRC-1 polypeptide (e.g., comprising 50, 60, 70, 80, 90 or 99% sequence identity or similarity) wherein said polypeptide comprises any detectable level of PXR or SRC-1 activity. For example, wherein the polypeptide comprises a detectable level of SR12813 binding activity or ABCB1 activating activity. Any polynucleotide encoding such a polypeptide is also within the scope of the present invention.

Assays

The PXR peptides of the invention can be used in assays for the identification of modulators of PXR (e.g., agonists or antagonists); modulators of CYP3A4 activation, and modulators of drug in vivo half-life. The assays set forth herein provide a convenient and cheap in vitro method by which it can be determined if the in vivo half life of a substance (e.g., a clinical drug candidate) will be modulated by cytochrome P450 enzymes such as CYP3A4 and by the multidrug resistant gene ABCB1.

In an embodiment of the assay methods set forth herein, PXR or the fragment thereof (e.g., SEQ ID NO: 1 or 2) is provided with SRC-1 or a fragment thereof (e.g., SEQ ID NO: 35). In an embodiment, PXR or the fragment thereof is fused to SRC-1 or the fragment thereof (e.g., by a polypeptide linker); in another embodiment, they are unfused.

The binding of a substance to be tested for the presence of a PXR agonist or antagonist can be monitored by temperature-dependent circular dichroism. Circular dichroism is observed when optically active matter (e.g., protein) absorbs left and right hand circular polarized light slightly differently. In an embodiment, it is measured with a CD spectropolarimeter. Generally, the instrument needs to be able to measure accurately in the far UV at wavelengths down to 190-170 nm. In addition, the difference in left and right handed absorbance A(l)-A(r) is very small corresponding to an ellipticity of a few 1/1000th of a degree (mdeg). The CD is a function of wavelength. The analysis of temperature-dependent circular dichroism spectra therefore yields valuable information about secondary structure of biological macromolecules as well as the melting temperature (Tm) of the substance being analyzed. Generally, the temperature-dependent circular dichroism spectrum of a given substance takes a sigmoidal shape and the melting temperature of the substance is the point of inflection on the sigmoid curve. Changes in PXR secondary structure can be monitored over a range of temperatures using temperature-dependent circular dichroism. As temperature increases, the temperature-dependent circular dichroism spectra of the protein and/or the Tm will change. Binding of modulators to PXR can be monitored by comparing the temperature-dependent circular dichroism spectrum and/or Tm of native PXR to that of PXR that has been contacted with a substance to be tested for the presence of a modulator. Specifically, a change in the PXR temperature-dependent circular dichroism spectra and/or Tm, in the presence of a substance being tested for the presence of a modulator, as compared to the temperature-dependent circular dichroism spectra of native PXR, will indicate PXR/modulator binding.

In an embodiment of the invention, a method for identifying a modulator or binder of PXR (e.g., agonist or antagonist); a modulator of CYP3A4 activation or a modulator of drug in vivo half-life comprises:

-   -   (a) contacting a composition comprising PXR or a fragment or         fusion thereof and SRC-1 or a fragment of fusion thereof (e.g.,         PXR-LBD; PXR_(full)linker-SRC or PXR-LBD-linker-SRC) with a         substance to be tested for the presence of the modulator or         binder (e.g., agonist or antagonist);     -   (b) determining the ellipticity of said composition;         whereby the substance is selected if the ellipticity and/or the         Tm of said composition alone is different from the ellipticity         and/or Tm of the composition that is in contact with said         substance.

In an embodiment of the invention, ellipticity is measured at several different temperatures (e.g., between 30° C. and 80° C.). The substance is determined to contain a modulator of PXR if the profile that is generated in the presence of the substance is different from the profile that is generated in the absence of the substance.

In an embodiment of the invention, the temperature-dependent circular dichroism assay is performed along with a negative-control method comprising:

-   -   (a) contacting a composition comprising PXR or a fragment or         fusion thereof and SRC-1 or a fragment of fusion thereof (e.g.,         PXR-LBD; PXR_(full)-linker-SRC or PXR-LBD-linker-SRC) with a         negative-control substance known not to contain a modulator or         binder of PXR; and     -   (b) determining the ellipticity of the composition and said         negative-control substance;         whereby the method is determined to be functioning properly if         the ellipticity and/or Tm of the composition alone is         essentially the same as that of the composition that is in         contact with the negative-control substance.

In an embodiment of the invention, the temperature-dependent circular dichroism assay is performed along with a positive-control method comprising:

-   -   (a) contacting a composition comprising PXR or a fragment or         fusion thereof and SRC-1 or a fragment of fusion thereof (e.g.,         PXR-LBD; PXR-linker-SRC or PXR-LBD-linker-SRC) with a         positive-control substance known to contain a modulator or         binder of PXR (e.g., SR12813, hyperforin, clotrimazole,         sulfopyrole or pregnane 16α-carbonitrile); and     -   (b) determining the ellipticity of the composition and said         positive-control substance;         whereby the method is determined to be functioning properly if         the ellipticity and/or Tm of the composition alone is different         from that of the composition that is in contact with the         positive-control substance.

The temperature-dependent circular dichroism methods set forth above can be modified to replace temperature variation with the addition of some other stimulus that affects PXR secondary structure. For example, instead of measuring ellipticity at various temperatures, ellipticity can be measured at different concentrations of protein denaturant. For example, the protein denaturants urea or guanidine HCl can be used.

Modulators or binders of PXR (e.g., agonist or antagonist); modulators of CYP3A4 activation and modulators of drug in vivo half-life can also be identified by direct binding assay. For example, in an embodiment of the invention, a method for identifying a modulator or binder (e.g., agonist or antagonist) of PXR or a fragment or fusion thereof (e.g., PXR-LBD; PXR_(full)linker-SRC or PXR-LBD-linker-SRC); a modulator of CYP3A4 activation or a modulator of drug in vivo half life comprises:

-   -   (1) contacting a composition comprising PXR or a fragment or         fusion thereof and SRC-1 or a fragment of fusion thereof with a         substance to be tested for the presence of a modulator or binder         (e.g., a detectably labeled substance); and     -   (2) determining if the substance binds to said PXR or fragment         or fusion thereof;         whereby the substance is selected if binding is observed.

In an embodiment of the invention, the direct binding assay is performed along with a negative-control assay comprising:

-   -   (1) contacting a composition comprising PXR or a fragment or         fusion thereof and SRC-1 or a fragment of fusion thereof with a         negative-control substance (e.g., a detectably labeled         negative-control substance) that is known not to comprise a         modulator or binder; and     -   (2) determining if the negative-control substance binds to said         PXR or fragment or fusion thereof;         whereby the method is determined to be functioning properly if         no direct binding of the negative-control substance is detected.

In an embodiment of the invention, the direct binding assay is performed along with a positive-control assay comprising:

-   -   (1) contacting a composition comprising PXR or a fragment or         fusion thereof and SRC-1 or a fragment of fusion thereof with a         positive-control substance (e.g., a detectably labeled         positive-control substance) that is known to comprise a         modulator (e.g., SR12813, hyperforin, clotrimazole, sulfopyrole         or pregnane 16α-carbonitrile); and     -   (2) determining if the positive-control substance binds to said         PXR or fragment or fusion thereof;         whereby the method is determined to be functioning properly if         direct binding of the positive-control substance is detected.

A substance being tested for the presence of a binder or modulator in any of the foregoing assays can be detectably labeled with any of many labels known in the art including, for example, 99Tc, ⁹⁰Y, ¹¹¹In, ³²P, ¹⁴C, ¹²⁵I, ³H, ¹³¹I, ¹¹C, ¹⁵O, ¹³N, ¹⁸F, ³⁵S, ⁵¹Cr, ⁵⁷To, ²²⁶Ra, ⁶⁰Co, ⁵⁹Fe, ⁵⁷Se, ¹⁵²Eu, ⁶⁷CU, ²¹⁷Ci, ²¹¹At, ²¹²Pb, ⁴⁷Sc, ¹⁰⁹Pd, ²³⁴Th, and ⁴⁰K, ¹⁵⁷Gd, ⁵⁵Mn, ⁵²Tr and ⁵⁶Fe. Such labels may be detected, e.g., in a scintillation counter when contacted with a scintillant.

In an embodiment of the invention, binding is determined by chromatographically binding the PXR/modulator or binder complex to a solid support, optionally washing the bound complex, optionally drying the washed complex (e.g., under a vacuum) and then detecting the presence of the modulator or binder on the support. In an embodiment, the solid support is a positively charged membrane or filter such as a nylon (e.g., Immobilon-Ny+ transfer membrane; Millipore; Billerica, Massachusetts).

Bound complex may be detected by any of several methods known in the art. For example, if the complex comprises a radiolabel (e.g., [³H]-SR12813), the bound complex can be detected chemilluminescently (e.g., using Opti-Fluor Scintillation cocktail; Perkin Elmer Life and Analytical Sciences, Inc.; Boston, Mass.). Chemilluminescence can be detected, for example, in a scintillation counter (Packard Top-counter). Specifically, the bound complex can be contacted with scintillant and then analyzed for the occurrence of scintillation.

In an embodiment of the invention, modulators or binders of PXR (e.g., agonist or antagonist); modulators of CYP3A4 activation and modulators of drug in vivo half-life can also be identified by competition or competitive inhibition assay. In a competition assay, a modulator or binder is identified based upon its ability to compete for binding with a substance known to bind PXR (this substance will be referred to as “ligand” for the purposes of discussing this method). In an embodiment, such a method comprises:

-   -   (i) contacting a composition comprising PXR or a fragment or         fusion thereof and SRC-1 or a fragment of fusion thereof with a         ligand that is known to bind said PXR or said fragment or fusion         thereof and with a substance to be tested for the presence of a         modulator or binder; and     -   (ii) determining if the substance being tested reduces binding         of the ligand to the PXR or the fragment or fusion thereof;         whereby the substance is selected if binding of the ligand to         the PXR or the fragment or fusion thereof is reduced as compared         to ligand binding to PXR or the fragment or fusion thereof in         the absence of the substance.

During such a competition assay, a complex between PXR or a fragment or fusion thereof and said ligand is formed. Such a complex is within the scope of and forms a part of the present invention. For example, the scope of the present invention includes complexes comprising PXR, PXR-LBD, PXR_(full)linker-SRC or PXR-LBD-linker-SRC bound to SR12813, hyperforin, clotrimazole, sulfopyrole, pregnane 16α-carbonitrile or any other substance, known in the art, to bind to PXR.

In an embodiment of the invention, the competition assay is performed along with a positive-control assay. In an embodiment, such a positive-control assay comprises:

-   -   (i) contacting a composition comprising PXR or a fragment or         fusion thereof and SRC-1 or a fragment of fusion thereof with a         ligand that is known to bind PXR or said fragment or fusion         thereof with a positive-control substance known to bind to PXR         or a fragment or fusion thereof; and     -   (ii) determining if said positive-control substance reduces the         binding of the ligand;         whereby the assay is determined to function properly if the         binding of said ligand is reduced.

In an embodiment of the invention, the competition assay is performed along with a negative-control assay. In an embodiment, such a negative-control assay comprises:

-   -   (i) contacting a composition comprising PXR or a fragment or         fusion thereof and SRC-1 or a fragment of fusion thereof with a         ligand that is known to bind the PXR or said fragment or fusion         thereof and with a negative-control substance known not to bind         to the PXR or a fragment or fusion thereof; and     -   (ii) determining if said negative-control substance reduces that         binding of said ligand;         whereby the assay is determined to function properly if the         binding of said ligand is not reduced.

The term “ligand” includes any substance that is known to bind to PXR including, but not limited to, SR12813, hyperforin, clotrimazole, ritonavir, sulfopyrole, pregnane-16α-carbonitrile, RU-486, rifampicin, dexamethasone, paclitaxel, metyrapone, bisphenol A, diethylhexylphthalate, nonylphenol, phthalate, cisplatin, chenodeoxycholic acid, deoxycholic acid, lithocholic acid, 17β-estradiol (estradiol), pregnenolone (5-pregneno-3β-ol-20-one), progesterone and Medroxyprogesterone-acetate (MPA) as well as radiolabeled versions of any of the foregoing.

Any of several method known in the art can be used to determine the binding of the ligand. For example, in an embodiment of the invention, a method similar to that employed in the direct binding assays set forth herein is used. In this embodiment of the invention, the ligand is detectably labeled (e.g., with a radiolabel such as ³H) and its binding is detected chromatographically. For example, PXR/ligand complexes can be bound to a solid matrix (e.g., a charged membrane), optionally washed and analyzed for the presence of the radiolabel (e.g., by scintillation).

In an embodiment of the invention, the K_(i) value is calculated by the equation set forth in Cheng & Prusoff (Biochem. Pharmacol. 22:3099, 1973): K_(i)=IC₅₀/1+([L]/K_(d)) in which IC₅₀ value is that concentration (nM) of test substance by which 50% of specific labeled ligand is displaced from PXR, [L] is the concentration of the specific labeled ligand in the assay and the K_(d) is the affinity of radioligand for the receptor.

Modulators of PXR can also be identified using a cell-based assay. An activity of PXR is transcriptional activation of the CYP3A4 gene (Kliewer et al., Cell 92: 73-82 (1998); Lehmann et al., J Clin Invest 102: 1016-1023 (1998); Bertilsson et al., Proc Natl Acad Sci USA 95: 12208-12213 (1998); Pascussi et al., Biochem Biophys Res Commun 260: 377-381 (1999) or the multidrug resistance gene ABCB1 (Synold et al., Nature Med. 7: 584-590 (2001); Geick et al., J. Biol. Chem. 276: 14581-14587 (2001)). Agonism or antagonism of PXR can be observed by monitoring the transcriptional activation of the gene. For example, in an embodiment of the invention, a method for identifying a modulator (e.g., agonist or antagonist) of PXR or a fragment or fusion thereof (e.g., PXR-LBD; PXR-linker-SRC or PXR-LBD-linker-SRC); a modulator of CYP3A4 activation or a modulator of drug half-life comprises:

-   -   (A) contacting an isolated host cell comprising PXR or a         fragment or fusion thereof (e.g., PXR-LBD; PXR-linker-SRC or         PXR-LBD-linker-SRC) and SRC-1 or a fragment of fusion thereof         and a reporter gene operably linked to a CYP3A4 promoter or to         an ABCB1 promoter with a substance to be tested for the presence         of a modulator; and     -   (B) determining if the reporter gene is expressed;         whereby the substance is selected if the reporter gene, in the         cell contacted with said substance, is expressed at a higher or         lower level than a reporter gene in a host cell that is not         contacted with said substance. If the reporter gene is expressed         at a lower level, the substance is identified as containing an         antagonist and if the reporter gene is expressed at a higher         level, the substance is identified as containing an agonist.

In an embodiment of the invention, the cell based method is performed along with a negative-control method comprising:

-   -   (A) contacting an isolated host cell comprising PXR or a         fragment or fusion thereof (e.g., PXR-LBD; PXR-linker-SRC or         PXR-LBD-linker-SRC) and SRC-1 or a fragment of fusion thereof         and a reporter gene operably linked to a CYP3A4 promoter or to         an ABCB1 promoter with a negative-control substance known not to         comprise a modulator; and     -   (B) determining if the reporter gene is expressed;         whereby the method is determined to be functioning properly if a         basal level of reporter gene expression is observed in the         presence of the negative-control method.

In an embodiment of the invention, the cell based method is performed along with a positive-control method comprising:

-   -   (A) contacting an isolated host cell comprising PXR or a         fragment or fusion thereof (e.g., PXR-LBD; PXR-linker-SRC or         PXR-LBD-linker-SRC) and SRC-1 or a fragment of fusion thereof         and a reporter gene operably linked to a CYP3A4 promoter or to         an ABCB1 promoter with a positive-control substance known to         comprise a modulator (e.g., SR12813, hyperforin, clotrimazole,         sulfopyrole or pregnane 16α-carbonitrile); and     -   (B) determining if the reporter gene is expressed;         whereby the method is determined to be functioning properly if         the level of reporter gene expression observed in the presence         of the positive-control substance is greater than a basal level         of reporter gene expression.

A host cell that can be used in the cell-based assay can be any cell type. In an embodiment, the host cell is a mammalian cell such as a HepG2 cell.

In an embodiment of the invention, the reporter gene is, for example, green fluorescent protein (GFP); Renilla luciferase (see e.g., Genbank Accession Nos.: AF416990; AR149562; AF362548 or M63501), firefly (Photinus pyralis) luciferase (see e.g., Genbank Accession Nos.: U03687; M15077 and X84846), E. coli lacZ Aequorea Victoria aequorin, human alkaline phosphatase or E. coli β-lactamase. In an embodiment of the invention, chloramphenicol acetyltransferase (CAT) is used as a reporter gene. CAT radioassays are described, for example, by Sleigh (Anal. Biochem. 156(1):251-256 (1986)) and a non-radioactive CAT assay is described by Young et al. (Anal. Biochem. 197(2):401-407 (1991)). In an embodiment of the invention, GFP is green fluorescent protein (GFP) isolated from Aequorea victoria (Chalfie et al. Science 263, 802-805 (1994)) is the reporter gene. In an embodiment of the invention, firefly luciferase reporter gene that has been altered as described in Leskinen et al. (Yeast. 20(13):1109-1113 (2003)) wherein the carboxy-terminal peroxisomal targeting signal, Ser-Lys-Leu (slk), of the firefly luciferase gene was removed is the reporter gene.

Crystals

Crystallization may be accomplished by using a number of methods (See e.g., Giegé, et al., (1994) Acta Crystallogr. D50: 339-350; McPherson, (1990) Eur. J. Biochem. 189: 1-23). Such techniques include microbatch, hanging drop, seeding and dialysis. Hanging-drop vapor diffusion (McPherson, (1976) J. Biol. Chem. 251: 6300-6303) or microbatch method (Chayen (1997) Structure 5: 1269-1274) is used in an embodiment of the invention. In each of these methods, it is important to promote continued crystal growth after nucleation by maintaining a supersaturated solution. In the microbatch method, polypeptide is mixed with precipitants to achieve supersaturation, the vessel is sealed and set aside until crystals appear. In the dialysis method, polypeptide is retained in a sealed dialysis membrane which is placed into a solution containing precipitant. Equilibration across the membrane increases the precipitant concentration thereby causing the polypeptide to reach supersaturation levels. It is desirable to use a PXR protein preparation having a concentration of at least about 1 mg/mL and preferably about 10 mg/mL to about 20 mg/mL. It may also be desirable to include a protein stabilizing agent.

The crystals of the present invention have a wide range of uses. For example, high quality crystals are suitable for X-ray or neutron diffraction analysis to determine the three dimensional structure of PXR or a fragment or fusion thereof (e.g., PXR-LBD-linker-SRC-1) and in particular to assist in the identification of the protein's active and effector sites. Knowledge of these sites and solvent accessible residues allow structure-based design and construction of agonists and antagonists for PXR as well as development of drugs do not interact with PXR and have low incidence of side-effects.

In addition, crystallization itself can be used as a purification method. In some instances, a polypeptide or protein crystallizes from a heterogeneous mixture into crystals. Isolation of such crystals by filtration and/or centrifugation, followed by redissolving the polypeptide affords a purified solution suitable for use in growing high-quality crystals which are preferred for diffraction analysis. Such a method forms part of the present method.

Once a crystal of the present invention is grown, X-ray diffraction data can be collected. One method for determining structure with X-ray diffraction data includes use of synchrotron radiation, under standard cryogenic condition; however, alternative methods may also be used. For example, crystals can be characterized by using X-rays produced by a conventional source, such as a sealed tube or a rotating anode. Methods of characterization include, but are not limited to, precession photography, oscillation photography and diffractometer data collection.

The crystallizable compositions provided by this invention are amenable to X-ray crystallography for providing the three-dimensional structure of a PXR or a fragment or fusion thereof (e.g., PXR-LBD-linker-SRC-1). The present invention includes crystals which effectively diffract X-rays for the determination of the atomic coordinates of PXR or a fragment or fusion thereof (e.g., PXR-LBD-linker-SRC-1) to a resolution of greater than about 5.0 Ångströms (e.g., about 4.5 Å, about 4.0 Å, about 3 Å, about 2.5 Å, about 2 Å, about 1 Å), preferably greater than about 4.0 Ångströms (e.g., about 3 Å, about 2.5 Å, about 2 Å, about 1 Å), more preferably greater than about 2.8 Ångströms (e.g., about 2.5 Å, about 2 Å, about 1 Å).

The present invention includes PXR crystals (e.g., PXR-LBD-linker-SRC-1) whose three-dimensional structure is described by the structure coordinates set forth herein, e.g., in Tables 3 and 4 and 5 (e.g., 3a, 3b, 3c, 4a, 4b, 5a, 5b, 5c, 5d). The scope of the present invention also includes crystals that possess structural coordinates which are similar to those set forth herein, e.g., in Tables 3 and 4 and 5 (e.g., 3a, 3b, 3c, 4a, 4b, 5a, 5b, 5c, 5d); in an embodiment, the crystals or the soluble polypeptides which are used to form the crystals exhibit PXR activity (e.g., binding to SR12813, hyperforin or pregnane 16α-carbonitrile). In an embodiment, the crystals include a polypeptide which includes the amino acid sequence of any of SEQ ID NOs: 1, 2, 22, 24, 26, 28, 30 or 32. Structural similarity between crystals is discussed in detail below.

In an embodiment of the invention, a crystal of the invention comprises a tetragonal space group containing one monomer per asymmetric unit or an orthorhombic space group containing two monomers per asymmetric unit.

The term “structure coordinates” refers to Cartesian coordinates derived from mathematical equations related to the patterns obtained on diffraction of a beam of X-rays by the atoms (scattering centers) of a molecule. The diffraction data are used to calculate electron density maps and to establish the positions of the individual atoms of the molecule.

Those of skill in the art will understand that a set of structure coordinates for an enzyme or an enzyme-complex or a portion thereof, is a relative set of points that define a shape in three dimensions. Thus, it is possible that an entirely different set of coordinates could define a similar or identical shape. Moreover, slight variations in the individual coordinates may have little effect on overall shape.

The present invention includes crystals (e.g., PXR-LBD-linker-SRC-1) exhibiting structural coordinates which are similar to those set forth herein, e.g., in Tables 3 and 4 and 5 (e.g., 3a, 3b, 3c, 4a, 4b, 5a, 5b, 5c, 5d) but for crystallographic permutations of the structure coordinates, fractionalization of the structure coordinates, additions, subtractions, rotations or translations to sets of the structure coordinates or any combinations of the above.

Modifications in the crystal structure due to mutations, additions, substitutions, and/or deletions of amino acids, or other changes in any of the components that make up the crystal may account for variations in structure coordinates. If such variations are within an acceptable standard error as compared to the coordinates of Tables 3 and 4 and 5 (e.g., 3a, 3b, 3c, 4a, 4b, 5a, 5b, 5c, 5d), the resulting three-dimensional shape is considered to be the same and, accordingly, the modified crystal is considered to be within the scope of the present invention.

Various computational analyses may be necessary to determine whether a crystal is sufficiently similar to the crystals whose structural coordinates are set forth in Tables 3 and 4 and 5 (e.g., 3a, 3b, 3c, 4a, 4b, 5a, 5b, 5c, 5d) as to be considered the same. Such analyses may be carried out in current software applications, such as the Molecular Similarity application of QUANTA (Molecular Simulations Inc., San Diego, Calif.) version 4.1, and as described in the accompanying User's Guide.

The Molecular Similarity application permits comparisons between different structures, different conformations of the same structure, and different parts of the same structure. In general, the procedure used in Molecular Similarity to compare structures is divided into four steps: 1) input the structures to be compared; 2) define the atom equivalences in these structures; 3) perform a fitting operation; and 4) analyze the results.

Each structure is identified by a name. One structure is identified as the target (i.e., the fixed structure); all remaining structures are working structures (i.e., moving structures). Since atom equivalency within QUANTA is defined by user input, for the purpose of this invention we will define equivalent atoms as protein backbone atoms (N, Cα, C and O) for all conserved or common residues between the two structures being compared.

When a rigid fitting method is used, the working structure is translated and rotated to obtain an optimum fit with the target structure. The fitting operation uses a least squares fitting algorithm that computes the optimum translation and rotation to be applied to the moving structure, such that the root mean square difference of the fit over the specified pairs of equivalent atom is an absolute minimum. This number, given in Ångströms, is reported by QUANTA.

The term “root mean square deviation” (RMSD) is a commonly known term in the art which, in general, means the square root of the arithmetic mean of the squares of the deviations from the mean distance of corresponding atoms. It is a way to express the deviation or variation from a trend or object.

For the purpose of this invention, any crystalline molecule characterized by a set of structure coordinates that has a RMSD of conserved or common residue backbone atoms (N, Cα, C, O) or of only alpha carbon atoms of less than about 1.5 Å when superimposed—using backbone atoms or alpha carbon atoms (Cα)—on the relevant structure coordinates of Table 3 or 4 or 5 (e.g., any monomer of PXR-LBD-linker-SRC-1 as set forth in Table 3a, 3b, 4a, 5a or 5b) are considered identical and are within the scope of the present invention. In an embodiment, the root mean square deviation is less than about 1.0 Å (e.g., 0.9 Å, 0.8 Å, 0.7 Å, 0.6 Å), less than about 0.5 (e.g., 0.4 Å, 0.3 Å), less than about 0.25 Å (e.g., 0.2 Å, 0.15 Å) or less than about 0.1 Å.

The term “least squares” refers to a method based on the principle that the best estimate of a value is that in which the sum of the squares of the deviations of observed values is a minimum.

Computers

In accordance with the present invention, the structure coordinates of PXR-linker-SRC1 fusion polypeptide and portions thereof may be stored in a machine-readable storage medium. Such data may be used for a variety of purposes, such as drug discovery and x-ray crystallographic analysis of a protein crystal (e.g., for producing a three-dimensional representation of PXR). Accordingly, one aspect of this invention provides a machine-readable data storage medium comprising a data storage material encoded with the structure coordinates set forth in Table 3, 4, or 5 (e.g., 3a, 3b, 3c, 4a, 4b, 5a, 5b, 5c, 5d). The machine-readable data storage medium may also include any set of structure coordinates of a molecule that has a root mean square deviation of conserved or common residue backbone atoms (N, Cα, C, O) or only alpha carbon atoms (Cα) of less than about 1.5 Å, preferably, less than about 1.0 Å, more preferably less than about 0.5 Å and even more preferably less than about 0.1 Å when superimposed—using backbone atoms or alpha carbon atoms—on the relevant structure coordinates of Table 3, 4, or 5 (e.g., 3a, 3b, 3c, 4a, 4b, 5a, 5b, 5c, 5d).

A computer system, useful in reading the machine readable data storage medium, includes a computer comprising a central processing unit (“CPU”) and a memory storage device and is also within the scope of the present invention. In general, the computer system may be any computer with an operating system such as MS-DOS, PC-DOS, Windows, OS/2, Unix, Unix variant or MacOS. Particularly preferred computer systems are the Silicon Graphics Octane workstation or Compaq AlphaServer DS20. Other hardware systems and software packages will be known to those skilled in the art.

Input hardware coupled to the computer system by input line, may be implemented in a variety of ways. Machine-readable data of this invention may be input via the use of a modem or modems connected by a telephone line or a dedicated data line. Alternatively or additionally, the input hardware may comprise CD-ROM drives or disk drives. A keyboard may also be used as an input device.

Output hardware, coupled to the computer system by output lines, may similarly be implemented by conventional devices. By way of example, output hardware may include a display terminal (e.g., a cathode ray tube (CRT)) for displaying a graphical representation of the three dimensional structure of PXR or a portion thereof using a program such as INSIGHT (Molecular Simulations Inc., San Diego, Calif.) or QUANTA as described herein. Output hardware might also include a printer, so that hard copy output may be produced, or a disk drive, to store system output for later use. In preferred embodiments, the computer possesses a display which is displaying a three dimensional representation of PXR or a fragment or homologue thereof.

In operation, the central processing unit (CPU) coordinates the use of the various input and output devices, coordinates data accesses from mass storage and accesses to and from working memory, and determines the sequence of data processing steps. A number of programs may be used to process the machine-readable data of this invention. Such programs are discussed in reference to the computational methods of drug discovery as described herein. Specific references to components of the computer system are included as appropriate throughout the following description of the data storage medium.

A magnetic data storage medium can be encoded with a machine-readable data by a computer system as described above. Storage medium may be, for example, a conventional floppy diskette or hard disk, having a suitable substrate, which may be conventional, and a suitable coating, which may be conventional, on one or both sides, containing magnetic domains whose polarity or orientation can be altered magnetically. The magnetic domains of the coating of medium may be polarized or oriented so as to encode, in a mariner which may be conventional, machine readable data, such as that described herein, for execution by a system as described herein. Storage medium may also have an opening for receiving the spindle of a disk drive or other data storage device. Alternatively, an optically-readable data storage medium can be encoded with such machine-readable data, or a set of instructions. Medium can be a conventional compact disk read only memory (CD-ROM) or a rewritable medium such as a magneto-optical disk which is optically readable and magneto-optically writable.

In general, in the case of CD-ROM, as is well known, disk coating is reflective and is impressed with a plurality of pits to encode the machine-readable data. The arrangement of the pits is read by reflecting laser light off the surface of the coating. A protective coating, which preferably is substantially transparent, is provided on top of the coating.

In general, in the case of a magneto-optical disk, as is well known, disk coating has no pits, but has a plurality of magnetic domains whose polarity or orientation can be changed magnetically when heated above a certain temperature, as by a laser. The orientation of the domains can be read by measuring the polarization of laser light reflected from the coating. The arrangement of the domains encodes the data as described above.

Molecular Modeling

The present invention permits the use of structure-based drug design techniques to design, select, and synthesize chemical entities, including inhibitory compounds that are capable of binding to a PXR polypeptide or fusion thereof (e.g., PXR-linker-SRC-1). Also, de novo and iterative drug design methods can be used to develop drugs from the structure of the PXR crystals of this invention.

Specifically, the crystals of the invention can be used to identify modulators of PXR; modulators of CYP3A4 activation, and modulators of drug in vivo half life by use of molecular modeling techniques that are known in the art. Identification of modulators of PXR by molecular modeling provides a convenient and cheap method by which it can be determined if the in vivo half life of a substance (e.g., a clinical drug candidate) will be modulated by cytochrome P450 enzymes such as CYP3A4 and by the multidrug resistance gene ABCB1.

For example, an embodiment of the invention comprises a method for identifying a PXR agonist or antagonist comprising the steps of a) crystallizing PXR or a fragment thereof fused to SRC-1 or a fragment thereof (e.g., PXR-LBD-linker-SRC1) to form at least one crystal; b) irradiating the crystal produced by step (a) to obtain a diffraction pattern of said crystal; c) determining the atomic coordinates of the three-dimensional structure of the PXR or the fragment or fusion thereof from the diffraction pattern; d) using the atomic coordinates and one or more molecular modeling techniques to identify an agent that interacts with the PXR; and, optionally, e) determining if the agonist or antagonist increases or decreases the in vivo activation of cytochrome P450 enzymes or the multidrug resistance gene ABCB1, or modulates or binds to PXR or modulates drug half life; wherein the agonist or antagonist is selected if it increases or decreases the in vivo activation of cytochrome P450 enzymes or the multidrug resistance gene ABCB1, binds to or modulates PXR or modulates drug half life. In an embodiment of the invention, an agonist or antagonist identified in the present molecular modeling method (steps a-d) is further analyzed by any method set forth in the “Assays” or “Pharmacology” section herein, to determine if it is, for example, a modulator or binder of PXR, a modulator of CYP3A4 activation or a modulator of drug in vivo half life (step e).

The methods of the present invention can also be used to identify drug products that do not interact with PXR. For example, an embodiment of the invention comprises a method comprising the steps of a) crystallizing PXR or a fragment thereof fused to SRC1 or a fragment thereof and complexed with a candidate drug (e.g., a small organic molecule) to form at least one crystal; b) irradiating the crystal produced by step (a) to obtain a diffraction pattern of said crystal; c) determining the atomic coordinates of the three-dimensional structure of the PXR or the fragment or fusion thereof from the diffraction pattern; d) identifying interatomic interactions between the PXR and the candidate drug; and e) modifying the chemical structure of the candidate drug so as to eliminate or reduce that ability of the PXR and the candidate drug to bind.

The candidate drug can be a known substance that is known to interact with PXR or a new chemical entity. For example, in an embodiment of the invention, the drug candidate is SR12813 (or any other known PXR binding compound, e.g., as set forth herein) and the method is used to generate structural homologues of the compound which do not interact with PXR. The method optionally includes the step of performing in vitro or in vivo testing (e.g., a temperature dependent circular dichroism assay) of the modified drug candidate to assess its ability to interact with PXR.

One particularly useful drug design technique enabled by this invention is structure-based drug design. Structure-based drug design is a method for optimizing associations between a protein and a compound by determining and evaluating the three-dimensional structures of successive sets of protein/compound complexes.

Those skilled in the art will appreciate that association of natural ligands or substrates with the binding pockets of their corresponding receptors or enzymes is the basis of many biological mechanisms of action. The term “binding pocket” or “binding domain”, as used herein, includes any region of a molecule or molecular complex, that, as a result of its shape, favorably associates with another chemical entity or compound. Similarly, drugs may exert their biological effects through association with the binding pockets of receptors and enzymes. Such association may occur with all or any part of the binding pockets. An understanding of such associations will help lead to the design of drugs having more favorable associations with the target enzyme, and thus, improved biological effects. Therefore, this information is valuable in designing potential enzyme inhibitors, such as inhibitors of PXR.

In iterative structure-based drug design, crystals of a series of protein/compound complexes are obtained and then the three-dimensional structure of each complex is solved. Such an approach provides insight into the association between the proteins and compounds of each complex. This is accomplished by selecting compounds with inhibitory activity, obtaining crystals of a new polypeptide, solving the three-dimensional structure of the polypeptide, and comparing the associations between the new protein and previously solved protein. By observing how changes in the compound affected the protein/compound associations, these associations may be optimized.

In some cases, iterative structure-based drug design is carried out by forming successive protein-compound complexes and then crystallizing each new complex. Alternatively, a pre-formed protein crystal is soaked in the presence of an inhibitor, thereby forming a protein/compound complex and obviating the need to crystallize each individual protein/compound complex. Advantageously, PXR crystals provided by this invention may be soaked in the presence of a compound or compounds, such as PXR inhibitors, substrates or other ligands to provide novel PXR/compound crystal complexes. As used herein, the term “soaked” may refer to a process in which the crystal is transferred to a solution containing the compound of interest.

The structure coordinates set forth in Table 3, 4 or 5 (e.g., 3a, 3b, 3c, 4a, 4b, 5a, 5b, 5c, 5d) can also be used to aid in obtaining structural information about another crystallized molecule or molecular complex. This may be achieved by any of a number of well-known techniques, including molecular replacement.

The structure coordinates set forth in Table 3, 4 or 5 (e.g., 3a, 3b, 3c, 4a, 4b, 5a, 5b, 5c, 5d) can also be used for determining at least a portion of the three-dimensional structure of molecules or molecular complexes which contain at least some structurally similar features to PXR. In particular, structural information about another crystallized molecule or molecular complex may be obtained by well-known techniques, including molecular replacement.

Therefore, another aspect of this invention provides a method of utilizing molecular replacement to obtain structural information about a crystallized molecule or molecular complex, whose structure is unknown, comprising the steps of generating an x-ray diffraction pattern from said crystallized molecule or molecular complex and applying crystallographic phases derived from at least a portion of the structure coordinates set forth in Table 3, 4 or 5 (e.g., 3a, 3b, 3c, 4a, 4b, 5a, 5b, 5c, 5d) to the x-ray diffraction pattern to generate a three-dimensional electron density map of the molecule or molecular complex whose structure is unknown.

Once the structure coordinates of a protein crystal have been determined, they are useful in solving the structures of other crystals. In addition, the structure of PXR homologues may be determined from the structural coordinates of the present invention. For example, polypeptides may be crystallized and their structure elucidated by, for example, difference Fourier techniques and molecular replacement.

By using molecular replacement, all or part of the structure coordinates of the PXR polypeptide provided by this invention can be used to determine the previously unknown structure of a crystallized molecule or molecular complex more quickly and efficiently than attempting to determine such information ab initio.

Molecular replacement provides an accurate estimation of the phases for an unknown structure. Phases are a factor in equations used to solve crystal structures that cannot be measured experimentally. Obtaining accurate values for the phases, by methods other than molecular replacement, is a time-consuming process. However, when the crystal structure of a protein containing a homologous portion has been solved, the phases from the known structure may provide a satisfactory estimate of the phases for the unknown structure.

Thus, this method involves generating a preliminary model of a molecule or molecular complex whose structure coordinates are unknown, by orienting and positioning the relevant portion of the PXR crystal according to Table 3, 4 or 5 (e.g., 3a, 3b, 3c, 4a, 4b, 5a, 5b, 5c, 5d) within the unit cell of the crystal of the unknown molecule or molecular complex so as best to account for the observed x-ray diffraction pattern amplitudes to generate an election density map of the structure whose coordinates are unknown. This, in turn, can be subjected to any well-known model building and structure refinement techniques to provide a final, accurate structure of the unknown crystallized molecule or molecular complex (Lattman, “Use of the Rotation and Translation Functions”, in Meth. Enzymol., 115: 55-77 (1985); Rossman, ed., “The Molecular Replacement Method”, Int. Sci. Rev. Ser., No. 13, Gordon & Breach, New York (1972)).

Phase information from the structure coordinates of the present invention may be used to elucidate the structure of other crystals. For example, the structure of PXR in complex with other atoms or molecules may be elucidated. Such complexes include, for example, those containing atoms soaked into or cocrystallized within the crystal lattice. Other structures which can be elucidated using the phase information of the present invention include, for example, other PXR constructs or homologues or mutants thereof having sufficient three-dimensional structure similarity to a PXR complex as to be solved using molecular replacement. Also, these protein molecules, in a complex with a small molecule binder(s), agonist(s), antagonist(s), or analog(s) of any of these, may also be solved using the phase information of the present invention. Complexes containing a combination of the above molecules may also be solved using the phase information of the present invention.

The structure of any portion of any crystallized molecule or molecular complex that is sufficiently homologous to any portion of the PXR protein can be solved by this method. The difference Fourier method simply calculates an electron density map using phases calculated from the structure coordinates and observed diffraction amplitudes from a crystal of an unknown structure. This method is often used to solve structures of protein/ligand complexes where the ligand is small and does not affect the crystal form significantly.

In a preferred embodiment, the method of molecular replacement is utilized to obtain structural information about a molecule wherein the molecule comprises a PXR polypeptide complex. The structure coordinates of PXR provided by this invention are particularly useful in solving the structure of other crystal forms of PXR polypeptide complexes. This approach enables the determination of the optimal sites for interaction between chemical entities, including interaction of candidate inhibitors with PXR.

PXR crystals may be studied using well-known x-ray diffraction techniques and may be refined versus x-ray data to 3 Å resolution or better to an R_(free) value of about 0.40 or less using computer software such as X-PLOR (Yale University, 1992, distributed by Molecular Simulations, Inc.; see e.g., Blundell & Johnson, supra; Meth, Enzymol., vol. 114 & 115, H. W. Wyckoff et al., eds., Academic Press (1985)). This information may be used to optimize known PXR inhibitors and to design new PXR inhibitors.

The ligand binding pocket or cavity of PXR has been identified and characterized (Watkins et al., Science 292: 23229-2333 (2001); Xiao et al., Drug Metab. and Disposition 30(9): 951-956 (2002); Watkins et al., Curr. Op. Drug Disc. & Dev. 5(1): 150-158 (2002)). In an embodiment of the invention, the binding pocket of PXR comprises the following amino acid residues: L206; S208; L209; V211; L240; M243; A244; M246; S247; F251; F281; C284; Q285; F288; W299; Y306; L308; E321; M323; L324; H327; H407; R410; L411; I414; F420; M425 and F429. The location of such residues in the PXR-LBD-SRC1 polypeptides of the invention (e.g., PXR-LBD-L10-SRC1 (e.g., SEQ ID NO: 24)) can be observed in the structural coordinates set forth in Tables 3a, 3b, 4a, 5b or 5a. Accordingly, the present invention comprise methods for identifying whether a chemical entity will associate with the PXR ligand binding pocket defined by the structural coordinates of PXR-LBD-L10-SRC1 (e.g., SEQ ID NO: 24) amino acids L206; S208; L209; V211; L240; M243; A244; M246; S247; F251; F281; C284; Q285; F288; W299; Y306; L308; E321; M323; L324; H327; H407; R410; L411; I414; F420; M425 and F429 according to Table 3a, 3b, 4a, 5b or 5a; or b) a homologue of said molecule or molecular complex, wherein said homologue comprises a binding pocket that has a root mean square deviation from the backbone atoms of said amino acids of not more than 1.5 Å (e.g., 1.25 Å, 1.0 Å, 0.75 Å, 0.50 Å, 0.25 Å or 0.1 Å) comprising the steps of: (i) employing computational means to perform a fitting operation between the chemical entity and the binding pocket of the molecule or molecular complex; and (ii) analyzing the results of said fitting operation to quantify the association between the chemical entity and the binding pocket. If the chemical entity is determined to fit or be capable of binding the binding pocket, it can be further tested for the ability to bind PXR or a PXR-SRC1 hybrid polypeptide in vitro or in vivo, for example, using any of the assay methods set forth herein.

Another embodiment of the invention comprises a method for identifying a compound capable of associating with a molecule comprising a PXR-LBD-L10-SRC1 (e.g., SEQ ID NO: 24) binding pocket comprising the steps of: a) using the atomic coordinates of PXR-LBD-L10-SRC1 amino acids L206; S208; L209; V211; L240; M243; A244; M246; S247; F251; F281; C284; Q285; F288; W299; Y306; L308; E321; M323; L324; H327; H407; R410; L411; I414; F420; M425 and F429 according to Table 3a, 3b, 4a, 5b or 5a+a root mean square deviation from the backbone atoms of said amino acids of not more than 1.5 Å (e.g., 1.25 Å, 1.0 Å, 0.75 Å, 0.50 Å, 0.25 Å or 0.1 Å), to generate a three-dimensional structure of a molecule comprising a PXR-LBD-L10-SRC1-like binding pocket; b) employing said three-dimensional structure to design or select said compound; c) synthesizing said compound; and d) contacting said compound with said molecule to determine the ability of said compound to interact with said molecule.

Pharmacology

Evaluation of the interaction of PXR with clinical drug candidates provides a fast and convenient method by which to determine if the candidate is likely to exhibit undesirable pharmacological properties. For example, identification of a drug candidate/PXR interaction indicates that the drug may exhibit an undesirably short half-life in vivo, that the drug may cause other co-administered drugs to exhibit an undesirably short half-life in vivo or that the drug candidate would be likely to be metabolized, in vivo, by liver enzymes (e.g., cytochrome P450 enzymes) into potentially toxic prodrugs. Clinical drug candidates that are not likely to exhibit desirable pharmacologic characteristics in vivo can be quickly and conveniently identified, in vitro, before in vivo administration to humans or animals, using the methods set forth herein.

In an embodiment of the pharmacological assay methods set forth herein, PXR or the fragment thereof (e.g., SEQ ID NO: 1 or 2) is provided with SRC-1 or a fragment thereof (e.g., SEQ ID NO: 3 or 35). In an embodiment, PXR or the fragment thereof is fused to SRC-1 or the fragment thereof (e.g., by a polypeptide linker); in another embodiment, they are unfused.

The present invention provides a method for determining whether the half-life of a drug will be affected by the cytochome P450 pathway when administered to a subject in vivo, comprising:

-   -   (i) contacting PXR or a fragment or fusion thereof (e.g.,         PXR-linker-SRC-1) with the drug; and     -   (ii) determining whether the drug binds to PXR or the fragment         or fusion thereof or modulates PXR or the fragment or fusion         thereof;         whereby the half-life of the drug is determined to be affected         by the P450 pathway if said binding or modulation is observed.

The present invention provides a method for determining whether a first drug will affect the half-life of a second drug when co-administered to a subject in vivo comprising:

-   -   (i) contacting PXR or a fragment or fusion thereof (e.g.,         PXR-linker-SRC-1) with said first drug; and     -   (ii) determining whether said first drug binds to or modulates         PXR;         whereby the half-life of the second drug is determined to be         affected by co-administration with the first drug if said         binding or modulation is observed.

The present invention also provides a method for determining whether a drug will be metabolized, when administered to a subject in vivo, into a prodrug comprising

-   -   (i) contacting PXR or a fragment or fusion thereof (e.g.,         PXR-linker-SRC-1) with the drug; and     -   (ii) determining whether the drug binds to or modulates PXR;         whereby it is determined that the drug will be metabolized into         a prodrug if said binding or modulation is observed.

Binding or modulation of a drug with PXR or a fragment or fusion thereof can be determined by any of the methods set forth above under “Assays” including circular dichroism, a direct binding assay or a cell based assay.

Any drug can be analyzed using one of the methods set forth herein to determine if its half-life or metabolism is affected by PXR. Such drugs include, but are not limited to, mometasone furoate, loratadine, desloratadine, fexofenadine HCl, cetirizine HCl, temozolomide, ezetimibe, ciprofloxacin, ofloxacin, levofloxacin, norfloxacin, enoxacin, lomefloxacin, grepafloxacin, trovafloxacin, sparfloxacin, temafloxacin, moxifloxacin, gatifloxacin, gemifloxacin, garenoxacin, vardenafil HCl, sildenafil citrate, interferon-2a or 2b, PEG-interferon-2a or 2b, ribavirin, simvastatin, atorvastatin, lovastatin, fluvastatin and pravastatin.

Examples

The following examples are provided to more clearly describe the present invention and should not be construed to limit the scope of the invention. Any composition described herein forms part of the present invention as does any method described herein.

Example 1 Construction of E. coli Bicistron Expression Constructs for Human PXR

D14-PXR-RBS-SRC. Human PXR-LBD DNA fragment P1 (coding for an N-terminal 6× His and amino acid residues 130-434 of SEQ ID NO: 1) was amplified using the primers H6-hPXR(130)-F (5′CACCATGAAAAAAGGTCACCACCATCA CCATCACGGTAGTGAACGGACAGGGACTCAGC3′) (SEQ ID NO: 4) and PBC-PXR-R (5′ CAGCTACCTGTGATGCCGAACAAC3′) (SEQ ID NO: 5); human SRC-1 DNA fragment S1 (containing the amino acid residues 623-710) was amplified using the primers PBC-SRC-F (5′GTTGTTCGGCATCACAGGTAGCTGAATTC AAGAAGGAGATATACCATGAGTAAATACTCTCAAACCAGTCACA 3′) (SEQ ID NO: 6) and SRC710-R (5′CTAATCAGGCTCGACAGACAAAG 3′) (SEQ ID NO: 7). P1 and S1 were mixed at 1:1 ratio, and subsequent PCR was performed on this mixture using primers H6-hPXR(130)-F (5′ CACCATGAAAAAAGGTCACC ACCATCACCATCACGGTAGTGAACG GACAGGGACTCAGC 3′) (SEQ ID NO: 8) and SRC710-R (5′CTAATCAGGCTCGACAGACAAAG 3′) (SEQ ID NO: 9). The final PCR product containing P1, a ribosomal binding sequence (RBS) and S1 was ligated into a Gateway vector pENTR™/SD/D-TOPO® to obtain a plasmid TOPO-PXR-RBS-SRC following the manufacturer's protocol (Invitrogen, Carlsbad, Calif.). The expression plasmid D14-PXR-RBS-SRC was subsequently obtained from an LR in vitro recombination reaction by mixing plasmids TOPO-PXR-RBS-SRC and pDEST14 following the manufacturer's protocol (Invitrogen, Carlsbad, Calif.) and confirmed by DNA sequencing.

D14-SRC-RBS-PXR. Human SRC-1 DNA fragment S2 (coding for an N-terminal 6× His and amino acid residues 623-710 of SEQ ID NO: 3) was amplified using the primers PSRC-F (5′CACCAGTAAATACTCTCAAACCAGTCAC3′) (SEQ ID NO: 10) and PBC-SRC-R (5′ TCAGGCTCGACAGACAAAGTGGTG 3′) (SEQ ID NO: 11); human PXR DNA fragment P2 (containing the amino acid residues 130-434) was amplified using the primers PBC PXR-F (5′CACCACTTTGTCTGTCGAGCCTGATTGAATTCAAGAAG GAGATATACCATGAAAAAAGGTCACCACCATCACCATC 3′) (SEQ ID NO: 12) and hPXR(434)-R (5′ TTAGCTACCTGTGATGCCGAACAAC3′) (SEQ ID NO: 13). S2 and P2 were mixed at 1:1 ratio, and subsequent PCR was performed on this mixture using primers PSRC-F (5′CACCAGTAAATACTCTCAAACCAGTCAC3′) (SEQ ID NO: 10) and hPXR(434)-R (5′TTAGCTACCTGTGATGCCGAACAAC3′) (SEQ ID NO: 13). The final PCR product was cloned into the vector pDEST14 to obtain the expression plasmid D14-SRC-RBS-PXR using the Gateway cloning strategy as described above (Invitrogen, Carlsbad, Calif.) and confirmed by DNA sequencing, respectively, by a PCR reaction using primers H6-hPXR(130)-F (5′CACCATGAAAAAAGGTCACCACCATCACCATCACGGTAGTGAA CGGACAGGGACTCAGC 3′) (SEQ ID NO: 4) and PL10-SRC-R (5′ TTATGAGGGGCTACCCTCCTGTAAGAGCCGGTGTAGAATTTTATGCCGTTCTGTCA ATGAGCTATGAGAAGAGCCACCAGAGCCACCGCTACCTGTGATGCCGAACAACTC 3′) (SEQ ID NO: 14). The resulting PCR product was cloned into the vector pDEST14 to obtain the expression plasmid D14-PXR-L10-SRCp using the Gateway cloning strategy as described above (Invitrogen, Carlsbad, Calif.) and confirmed by DNA sequencing.

The expression cassettes created in the two foregoing plasmids are represented, diagrammatically below:

PXR-RBS-SRC: --PXR(130-434 of SEQ ID NO: 1)→TGAATTCAAGAAGGAGATA TACC (SEQ ID NO: 15; Shine-Delgarno in bold font)--SRC (623-767 of SEQ ID NO: 3)→ SRC-RBS-PXR: --SRC (623-767 of SEQ ID NO: 3)→TGAATTCAAGAAGGAGA TATACC (SEQ ID NO: 15; Shine-Delgarno in bold font)-- PXR (130-434 OF SEQ ID NO: 1)→

The nucleotide sequence of the PXR-LBD-RBS-SRC bicistronic construct was:

(SEQ ID NO: 16) atgaaaaaaggtcaccaccatcaccatcacggtagtgaacggacagggactcagccactgggagtgcaggggctg acagaggagcagcggatgatgatcagggagctgatggacgctcagatgaaaacctttgacactaccttctcccat ttcaagaatttccggctgccaggggtgcttagcagtggctgcgagttgccagagtctctgcaggccccatcgagg gaagaagctgccaagtggagccaggtccggaaagatctgtgctctttgaaggtctctctgcagctgcggggggag gatggcagtgtctggaactacaaacccccagccgacagtggcgggaaagagatcttctccctgctgccccacatg gctgacatgtcaacctacatgttcaaaggcatcatcagctttgccaaagtcatctcctacttcagggacttgccc atcgaggaccagatctccctgctgaagggggccgctttcgagctgtgtcaactgagattcaacacagtgttcaac gcggagactggaacctgggagtgtggccggctgtcctactgcttggaagacactgcaggtggcttccagcaactt ctactggagcccatgctgaaattccactacatgctgaagaagctgcagctgcatgaggaggagtatgtgctgatg caggccatctccctcttctccccagaccgcccaggtgtgctgcagcaccgcgtggtggaccagctgcaggagcaa ttcgccattactctgaagtcctacattgaatgcaatcggccccagcctgctcataggttcttgttcctgaagatc atggctatgctcaccgagctccgcagcatcaatgctcagcacacccagcggctgctgcgcatccaggacatacac ccctttgctacgcccctcatgcaggagttgttcggcatcacaggtagctgaattcaagaaggagatataccatga gtaaatactctcaaaccagtcacaaactagtgcagcttttgacaacaactgccgaacagcagttacggcatgctg atatagacacaagctgcaaagatgtcctgtcttgcacaggcacttccaactctgcctctgctaactcttcaggag gttcttgtccctcttctcatagctcattgacagaacggcataaaattctacaccggctcttacaggagggtagcc cctcagatatcaccactttgtctgtcgagcctgattaggcttggatcc

The nucleotide sequence of the SRC-RBS-PXR-LBD bicistronic construct was:

(SEQ ID NO: 17) atgagtaaatactctcaaaccagtcacaaactagtgcagcttttgacaacaactgccgaacagcagttacggcat gctgatatagacacaagctgcaaagatgtcctgtcttgcacaggcacttccaactctgcctctgctaactcttca ggaggttcttgtccctcttctcatagctcattgacagaacggcataaaattctacaccggctcttacaggagggt agcccctcagatatcaccactttgtctgtcgagcctgattgaattcaagaaggagatataccatgaaaaaaggtc accaccatcaccatcacggtagtgaacggacagggactcagccactgggagtgcaggggctgacagaggagcagc ggatgatgatcagggagctgatggacgctcagatgaaaacctttgacactaccttctcccatttcaagaatttcc ggctgccaggggtgcttagcagtggctgcgagttgccagagtctctgcaggccccatcgagggaagaagctgcca agtggagccaggtccggaaagatctgtgctctttgaaggtctctctgcagctgcggggggaggatggcagtgtct ggaactacaaacccccagccgacagtggcgggaaagagatcttctccctgctgccccacatggctgacatgtcaa cctacatgttcaaaggcatcatcagctttgccaaagtcatctcctacttcagggacttgcccatcgaggaccaga tctccctgctgaagggggccgctttcgagctgtgtcaactgagattcaacacagtgttcaacgcggagactggaa cctgggagtgtggccggctgtcctactgcttggaagacactgcaggtggcttccagcaacttctactggagccca tgctgaaattccactacatgctgaagaagctgcagctgcatgaggaggagtatgtgctgatgcaggccatctccc tcttctccccagaccgcccaggtgtgctgcagcaccgcgtggtggaccagctgcaggagcaattcgccattactc tgaagtcctacattgaatgcaatcggccccagcctgctcataggttcttgttcctgaagatcatggctatgctca ccgagctccgcagcatcaatgctcagcacacccagcggctgctgcgcatccaggacatacacccctttgctacgc ccctcatgcaggagttgttcggcatcacaggtagctaa

Example 2 Construction of Tethered Expression Plasmids

A DNA fragment encoding PXR-LBD with an N-terminal 6× His tag, followed by a linker (GGSGG) (SEQ ID NO: 37) and a peptide fragment of SRC-1 (residues 678-710 of SEQ ID NO: 3) was amplified using the primers hPXR(130)-F (5′CACCATGAAAAAAGGTCACCACCATCACCATCACGGTAGTGAACGGACAGGGAC TCAGC 3′) (SEQ ID NO: 4) and PL10-SRC-R (5′TTATGAGGGGCTACCCTCCTG TAAGAGCCGGTGTAGAATTTTATGCCGTTCTGTCAATGAGCTATGAGAAGAGCCAC CAGAGCCACCGCTACCTGTGATGCCGAACAACTC3′) (SEQ ID NO: 14). The resulting PCR product was cloned into the vector pDEST14 to obtain the expression plasmid D14-PXR-L5-SRCp using the Gateway cloning strategy as described above (Invitrogen, Carlsbad, Calif.) and confirmed by DNA sequencing. D14-PXR-L10-SRCp was used as a template to create D14-PXR-L8-SRCp and D14-PXR-L13-SRCp (which encode 2 aa residues shorter or 3 longer in the translated linker region, respectively) with primer pairs L8-f (5′cacaggtagcggtggtggctcttctc3′) (SEQ ID NO: 18)/L8R (5′gagaagagccaccaccgctacctgtg3′) (SEQ ID NO: 19) and L13-F (5′GTAGCGGTGGCTCTGGTGGCTCCGGTGGTTCTTCTCATAGCTCATTGACAGAAC3′) (SEQ ID NO: 20)/L13-R (5′GTTCTGTCAATGAGCTATGAGAAGAACCACCGGAGCCACCAGAGCCACCGCTAC3′) (SEQ ID NO: 21), respectively, using the two-stage QuikChange site-directed mutagenesis protocol.

See protocol in Wang et at, Methods Mol. Biol. 182: 37-43 (2002)).

The amino acid sequence of the tethered human PXR-LBD-L8-SRC (the linker sequence is underscored) was:

(SEQ ID NO: 22) MKKGHHHHHHGSERTGTQPLGVQGLTEEQRMMIRELMDAQMKTFDTTFSH FKNFRLPGVLSSGCELPESLQAPSREEAAKWSQVRKDLCSLKVSLQLRGE DGSVWNYKPPADSGGKEIFSLLPHMADMSTYMFKGIISFAKVISYFRDLP IEDQISLLKGAAFELCQLRFNTVFNAETGTWECGRLSYCLEDTAGGFQQL LLEPMLKFHYMLKKLQLHEEEYVLMQAISLFSPDRPGVLQHRVVDQLQEQ FAITLKSYIECNRPQPAHRFLFLKIMAMLTELRSINAQHTQRLLRIQDIH PFATPLMQELFGITGSGGGSSHSSLTERHKILHRLLQEGSPS.

In an embodiment, a polynucleotide encoding PXR-LBD-L8-SRC is

(SEQ ID NO: 23) ATGAAAAAAGGTCACCACCATCACCATCACGGTAGTGAACGGACAGGGACTCAGCCACTGGGAGTGCAGGGGCTG ACAGAGGAGCAGCGGATGATGATCAGGGAGCTGATGGACGCTCAGATGAAAACCTTTGACACTACCTTCTCCCAT TTCAAGAATTTCCGGCTGCCAGGGGTGCTTAGCAGTGGCTGCGAGTTGCCAGAGTCTCTGCAGGCCCCATCGAGG GAAGAAGCTGCCAAGTGGAGCCAGGTCCGGAAAGATCTGTGCTCTTTGAAGGTCTCTCTGCAGCTGCGGGGGGAG GATGGCAGTGTCTGGAACTACAAACCCCCAGCCGACAGTGGCGGGAAAGAGATCTTCTCCCTGCTGCCCCACATG GCTGACATGTCAACCTACATGTTCAAAGGCATCATCAGCTTTGCCAAAGTCATCTCCTACTTCAGGGACTTGCCC ATCGAGGACCAGATCTCCCTGCTGAAGGGGGCCGCTTTCGAGCTGTGTCAACTGAGATTCAACACAGTGTTCAAC GCGGAGACTGGAACCTGGGAGTGTGGCCGGCTGTCCTACTGCTTGGAAGACACTGCAGGTGGCTTCCAGCAACTT CTACTGGAGCCCATGCTGAAATTCCACTACATGCTGAAGAAGCTGCAGCTGCATGAGGAGGAGTATGTGCTGATG CAGGCCATCTCCCTCTTCTCCCCAGACCGCCCAGGTGTGCTGCAGCACCGCGTGGTGGACCAGCTGCAGGAGCAA TTCGCCATTACTCTGAAGTCCTACATTGAATGCAATCGGCCCCAGCCTGCTCATAGGTTCTTGTTCCTGAAGATC ATGGCTATGCTCACCGAGCTCCGCAGCATCAATGCTCAGCACACCCAGCGGCTGCTGCGCATCCAGGACATACAC CCCTTTGCTACGCCCCTCATGCAGGAGTTGTTCGGCATCACAGGTAGCGGTGGCGGCTCTTCTCATAGCTCATTG ACAGAACGGCATAAAATTCTACACCGGCTCTTACAGGAGGGTAGCCCCTCATAA

The amino acid sequence of the tethered human PXR-LBD-L10-SRC (the linker sequence is underscored) was:

(SEQ ID NO: 24) MKKGHHHHHHGSERTGTQPLGVQGLTEEQRMMIRELMDAQMKTFDTTFSH FKNFRLPGVLSSGCELPESLQAPSREEAAKWSQVRKDLCSLKVSLQLRGE DGSVWNYKPPADSGGKEIFSLLPHMADMSTYMFKGIISFAKVISYFRDLP IEDQISLLKGAAFELCQLRFNTVFNAETGTWECGRLSYCLEDTAGGFQQL LLEPMLKFHYMLKKLQLHEEEYVLMQAISLFSPDRPGVLQHRVVDQLQEQ FAITLKSYIECNRPQPAHRFLFLKIMAMLTELRSINAQHTQRLLRIQDIH PFATPLMQELFGITG SGGSGGSSHS SLTERHKILHRLLQEGSPS

In an embodiment, a polynucleotide encoding PXR-LBD-L10-SRC is:

(SEQ ID NO: 25) ATGAAAAAAGGTCACCACCATCACCATCACGGTAGTGAACGGACAGGGACTCAGCCACTGGGAGTGCAGGGGCTG ACAGAGGAGCAGCGGATGATGATCAGGGAGCTGATGGACGCTCAGATGAAAACCTTTGACACTACCTTCTCCCAT TTCAAGAATTTCCGGCTGCCAGGGGTGCTTAGCAGTGGCTGCGAGTTGCCAGAGTCTCTGCAGGCCCCATCGAGG GAAGAAGCTGCCAAGTGGAGCCAGGTCCGGAAAGATCTGTGCTCTTTGAAGGTCTCTCTGCAGCTGCGGGGGGAG GATGGCAGTGTCTGGAACTACAAACCCCCAGCCGACAGTGGCGGGAAAGAGATCTTCTCCCTGCTGCCCCACATG GCTGACATGTCAACCTACATGTTCAAAGGCATCATCAGCTTTGCCAAAGTCATCTCCTACTTCAGGGACTTGCCC ATCGAGGACCAGATCTCCCTGCTGAAGGGGGCCGCTTTCGAGCTGTGTCAACTGAGATTCAACACAGTGTTCAAC GCGGAGACTGGAACCTGGGAGTGTGGCCGGCTGTCCTACTGCTTGGAAGACACTGCAGGTGGCTTCCAGCAACTT CTACTGGAGCCCATGCTGAAATTCCACTACATGCTGAAGAAGCTGCAGCTGCATGAGGAGGAGTATGTGCTGATG CAGGCCATCTCCCTCTTCTCCCCAGACCGCCCAGGTGTGCTGCAGCACCGCGTGGTGGACCAGCTGCAGGAGCAA TTCGCCATTACTCTGAAGTCCTACATTGAATGCAATCGGCCCCAGCCTGCTCATAGGTTCTTGTTCCTGAAGATC ATGGCTATGCTCACCGAGCTCCGCAGCATCAATGCTCAGCACACCCAGCGGCTGCTGCGCATCCAGGACATACAC CCCTTTGCTACGCCCCTCATGCAGGAGTTGTTCGGCATCACAGGTAGCGGTGGCTCTGGTGGCTCTTCTCATAGC TCATTGACAGAACGGCATAAAATTCTACACCGGCTCTTACAGGAGGGTAGCCCCTCATAA

The amino acid sequence of the tethered human PXR-LBD-L13-SRC (the linker sequence is underscored) was:

(SEQ ID NO: 26) MKKGHHHHHHGSERTGTQPLGVQGLTEEQRMMIRELMDAQMKTFDTTFSH FKNFRLPGVLSSGCELPESLQAPSREEAAKWSQVRKDLCSLKVSLQLRGE DGSVWNYKPPADSGGKEIFSLLPHMADMSTYMFKGIISFAKVISYFRDLP IEDQISLLKGAAFELCQLRFNTVFNAETGTWECGRLSYCLEDTAGGFQQL LLEPMLKFHYMLKKLQLHEEEYVLMQAISLFSPDRPGVLQHRVVDQLQEQ FAITLKSYIECNRPQPAHRFLFLKIMAMLTELRSINAQHTQRLLRIQDIH PFATPLMQELFGITGSGGSGGSGGSSHSSLTERHKILHRLLQEGSPS

In an embodiment,a polynucleotide encoding PXR-LBD-L13-SRC is:

(SEQ ID NO: 27) ATGAAAAAAGGTCACCACCATCACCATCACGGTAGTGAACGGACAGGGACTCAGCCACTGGGAGTGCAGGGGCTG ACAGAGGAGCAGCGGATGATGATCAGGGAGCTGATGGACGCTCAGATGAAAACCTTTGACACTACCTTCTCCCAT TTCAAGAATTTCCGGCTGCCAGGGGTGCTTAGCAGTGGCTGCGAGTTGCCAGAGTCTCTGCAGGCCCCATCGAGG GAAGAAGCTGCCAAGTGGAGCCAGGTCCGGAAAGATCTGTGCTCTTTGAAGGTCTCTCTGCAGCTGCGGGGGGAG GATGGCAGTGTCTGGAACTACAAACCCCCAGCCGACAGTGGCGGGAAAGAGATCTTCTCCCTGCTGCCCCACATG GCTGACATGTCAACCTACATGTTCAAAGGCATCATCAGCTTTGCCAAAGTCATCTCCTACTTCAGGGACTTGCCC ATCGAGGACCAGATCTCCCTGCTGAAGGGGGCCGCTTTCGAGCTGTGTCAACTGAGATTCAACACAGTGTTCAAC GCGGAGACTGGAACCTGGGAGTGTGGCCGGCTGTCCTACTGCTTGGAAGACACTGCAGGTGGCTTCCAGCAACTT CTACTGGAGCCCATGCTGAAATTCCACTACATGCTGAAGAAGCTGCAGCTGCATGAGGAGGAGTATGTGCTGATG CAGGCCATCTCCCTCTTCTCCCCAGACCGCCCAGGTGTGCTGCAGCACCGCGTGGTGGACCAGCTGCAGGAGCAA TTCGCCATTACTCTGAAGTCCTACATTGAATGCAATCGGCCCCAGCCTGCTCATAGGTTCTTGTTCCTGAAGATC ATGGCTATGCTCACCGAGCTCCGCAGCATCAATGCTCAGCACACCCAGCGGCTGCTGCGCATCCAGGACATACAC CCCTTTGCTACGCCCCTCATGCAGGAGTTGTTCGGCATCACAGGTAGCGGTGGCTCTGGTGGCTCCGGTGGTTCT TCTCATAGCTCATTGACAGAACGGCATAAAATTCTACACCGGCTCTTACAGGAGGGTAGCCCCTCATAA

The amino acid sequence of the tethered human PXR_(full)-L8-SRC (the linker sequence is underscored) was:

(SEQ ID NO: 28) MKKGHHHHHHEVRPKESWNHADFVHCEDTESVPGKPSVNADEEVGGPQIC RVCGDKATGYHFNVMTCEGCKGFFRRAMKRNARLRCPFRKGACEITRKTR RQCQACRLRKCLESGMKKEMIMSDEAVEERRALIKRKKSERTGTQPLGVQ GLTEEQRMMIRELMDAQMKTFDTTFSHFKNFRLPGVLSSGCELPESLQAP SREEAAKWSQVRKDLCSLKVSLQLRGEDGSVWNYKPPADSGGKEIFSLLP HMADMSTYMFKGIISFAKVISYFRDLPIEDQISLLKGAAFELCQLRFNTV FNAETGTWECGRLSYCLEDTAGGFQQLLLEPMLKFHYMLKKLQLHEEEYV LMQAISLFSPDRPGVLQHRVVDQLQEQFAITLKSYIECNRPQPAHRFLFL KIMAMLTELRSINAQHTQRLLRIQDIHPFATPLMQELFGITG SGGGSSHS SLTERHKILHRLLQEGSPS

In an embodiment, a polynucleotide encoding PXR_(full)-L8-SRC is:

(SEQ ID NO: 29) ATGAAAAAAGGTCACCACCATCACCATCACGGTGAGGTGAGACCCAAAGAAAGCTGGAACCATGCTGACTTTGTA CACTGTGAGGACACAGAGTCTGTTCCTGGAAAGCCCAGTGTCAACGCAGATGAGGAAGTCGGAGGTCCCCAAATC TGCCGTGTATGTGGGGACAAGGCCACTGGCTATCACTTCAATGTCATGACATGTGAAGGATGCAAGGGCTTTTTC AGGAGGGCCATGAAACGCAACGCCCGGCTGAGGTGCCCCTTCCGGAAGGGCGCCTGCGAGATCACCCGGAAGACC CGGCGACAGTGCCAGGCCTGCCGCCTGCGCAAGTGCCTGGAGAGCGGCATGAAGAAGGAGATGATCATGTCCGAC GAGGCCGTGGAGGAGAGGCGGGCCTTGATCAAGCGGAAGAAAAGTGAACGGACAGGGACTCAGCCACTGGGAGTG CAGGGGCTGACAGAGGAGCAGCGGATGATGATCAGGGAGCTGATGGACGCTCAGATGAAAACCTTTGACACTACC TTCTCCCATTTCAAGAATTTCCGGCTGCCAGGGGTGCTTAGCAGTGGCTGCGAGTTGCCAGAGTCTCTGCAGGCC CCATCGAGGGAAGAAGCTGCCAAGTGGAGCCAGGTCCGGAAAGATCTGTGCTCTTTGAAGGTCTCTCTGCAGCTG CGGGGGGAGGATGGCAGTGTCTGGAACTACAAACCCCCAGCCGACAGTGGCGGGAAAGAGATCTTCTCCCTGCTG CCCCACATGGCTGACATGTCAACCTACATGTTCAAAGGCATCATCAGCTTTGCCAAAGTCATCTCCTACTTCAGG GACTTGCCCATCGAGGACCAGATCTCCCTGCTGAAGGGGGCCGCTTTCGAGCTGTGTCAACTGAGATTCAACACA GTGTTCAACGCGGAGACTGGAACCTGGGAGTGTGGCCGGCTGTCCTACTGCTTGGAAGACACTGCAGGTGGCTTC CAGCAACTTCTACTGGAGCCCATGCTGAAATTCCACTACATGCTGAAGAAGCTGCAGCTGCATGAGGAGGAGTAT GTGCTGATGCAGGCCATCTCCCTCTTCTCCCCAGACCGCCCAGGTGTGCTGCAGCACCGCGTGGTGGACCAGCTG CAGGAGCAATTCGCCATTACTCTGAAGTCCTACATTGAATGCAATCGGCCCCAGCCTGCTCATAGGTTCTTGTTC CTGAAGATCATGGCTATGCTCACCGAGCTCCGCAGCATCAATGCTCAGCACACCCAGCGGCTGCTGCGCATCCAG GACATACACCCCTTTGCTACGCCCCTCATGCAGGAGTTGTTCGGCATCACAGGTAGCGGTGGCGGCTCTTCTCAT AGCTCATTGACAGAACGGCATAAAATTCTACACCGGCTCTTACAGGAGGGTAGCCCCTCATAA

The amino acid sequence of the tethered human PXR_(full)-L10-SRC (the linker sequence is underscored) was:

(SEQ ID NO: 30) MKKGHHHHHHEVRPKESWNHADFVHCEDTESVPGKPSVNADEEVGGPQIC RVCGDKATGYHFNVMTCEGCKGFFRRAMKRNARLRCPFRKGACEITRKTR RQCQACRLRKCLESGMKKEMIMSDEAVEERRALIKRKKSERTGTQPLGVQ GLTEEQRMMIRELMDAQMKTFDTTFSHFKNFRLPGVLSSGCELPESLQAP SREEAAKWSQVRKDLCSLKVSLQLRGEDGSVWNYKPPADSGGKEIFSLLP HMADMSTYMFKGIISFAKVISYFRDLPIEDQISLLKGAAFELCQLRFNTV FNAETGTWECGRLSYCLEDTAGGFQQLLLEPMLKFHYMLKKLQLHEEEYV LMQAISLFSPDRPGVLQHRVVDQLQEQFAITLKSYIECNRPQPAHRFLFL KIMAMLTELRSINAQHTQRLLRIQDIHPFATPLMQELFGITG SGGSGGSS HS SLTERHKILHRLLQEGSPS

In an embodiment, a polynucleotide encoding PXR_(full)-L10-SRC is:

(SEQ ID NO: 31) ATGAAAAAAGGTCACCACCATCACCATCACGGTGAGGTGAGACCCAAAGAAAGCTGGAACCATGCTGACTTTGTA CACTGTGAGGACACAGAGTCTGTTCCTGGAAAGCCCAGTGTCAACGCAGATGAGGAAGTCGGAGGTCCCCAAATC TGCCGTGTATGTGGGGACAAGGCCACTGGCTATCACTTCAATGTCATGACATGTGAAGGATGCAAGGGCTTTTTC AGGAGGGCCATGAAACGCAACGCCCGGCTGAGGTGCCCCTTCCGGAAGGGCGCCTGCGAGATCACCCGGAAGACC CGGCGACAGTGCCAGGCCTGCCGCCTGCGCAAGTGCCTGGAGAGCGGCATGAAGAAGGAGATGATCATGTCCGAC GAGGCCGTGGAGGAGAGGCGGGCCTTGATCAAGCGGAAGAAAAGTGAACGGACAGGGACTCAGCCACTGGGAGTG CAGGGGCTGACAGAGGAGCAGCGGATGATGATCAGGGAGCTGATGGACGCTCAGATGAAAACCTTTGACACTACC TTCTCCCATTTCAAGAATTTCCGGCTGCCAGGGGTGCTTAGCAGTGGCTGCGAGTTGCCAGAGTCTCTGCAGGCC CCATCGAGGGAAGAAGCTGCCAAGTGGAGCCAGGTCCGGAAAGATCTGTGCTCTTTGAAGGTCTCTCTGCAGCTG CGGGGGGAGGATGGCAGTGTCTGGAACTACAAACCCCCAGCCGACAGTGGCGGGAAAGAGATCTTCTCCCTGCTG CCCCACATGGCTGACATGTCAACCTACATGTTCAAAGGCATCATCAGCTTTGCCAAAGTCATCTCCTACTTCAGG GACTTGCCCATCGAGGACCAGATCTCCCTGCTGAAGGGGGCCGCTTTCGAGCTGTGTCAACTGAGATTCAACACA GTGTTCAACGCGGAGACTGGAACCTGGGAGTGTGGCCGGCTGTCCTACTGCTTGGAAGACACTGCAGGTGGCTTC CAGCAACTTCTACTGGAGCCCATGCTGAAATTCCACTACATGCTGAAGAAGCTGCAGCTGCATGAGGAGGAGTAT GTGCTGATGCAGGCCATCTCCCTCTTCTCCCCAGACCGCCCAGGTGTGCTGCAGCACCGCGTGGTGGACCAGCTG CAGGAGCAATTCGCCATTACTCTGAAGTCCTACATTGAATGCAATCGGCCCCAGCCTGCTCATAGGTTCTTGTTC CTGAAGATCATGGCTATGCTCACCGAGCTCCGCAGCATCAATGCTCAGCACACCCAGCGGCTGCTGCGCATCCAG GACATACACCCCTTTGCTACGCCCCTCATGCAGGAGTTGTTCGGCATCACAGGTAGCGGTGGCTCTGGTGGCTCT TCTCATAGCTCATTGACAGAACGGCATAAAATTCTACACCGGCTCTTACAGGAGGGTAGCCCCTCATAA

The amino acid sequence of the tethered human PXR_(full)-L13-SRC (the linker sequence is underscored) was:

(SEQ ID NO: 32) MKKGHHHHHHEVRPKESWNHADFVHCEDTESVPGKPSVNADEEVGGPQIC RVCGDKATGYHFNVMTCEGCKGFFRRAMKRNARLRCPFRKGACEITRKTR RQCQACRLRKCLESGMKKEMIMSDEAVEERRALIKRKKSERTGTQPLGVQ GLTEEQRMMIRELMDAQMKTFDTTFSHFKNFRLPGVLSSGCELPESLQAP SREEAAKWSQVRKDLCSLKVSLQLRGEDGSVWNYKPPADSGGKEIFSLLP HMADMSTYMFKGIISFAKVISYFRDLPIEDQISLLKGAAFELCQLRFNTV FNAETGTWECGRLSYCLEDTAGGFQQLLLEPMLKFHYMLKKLQLHEEEYV LMQAISLFSPDRPGVLQHRVVDQLQEQFAITLKSYIECNRPQPAHRFLFL KIMAMLTELRSINAQHTQRLLRIQDIHPFATPLMQELFGITG SGGSGGSG GSSHS SLTERHKILHRLLQEGSPS

In an embodiment, a polynucleotide encoding PXR_(full)-L13-SRC is:

(SEQ ID NO: 33) ATGAAAAAAGGTCACCACCATCACCATCACGGTGAGGTGAGACCCAAAGAAAGCTGGAACCATGCTGACTTTGTA CACTGTGAGGACACAGAGTCTGTTCCTGGAAAGCCCAGTGTCAACGCAGATGAGGAAGTCGGAGGTCCCCAAATC TGCCGTGTATGTGGGGACAAGGCCACTGGCTATCACTTCAATGTCATGACATGTGAAGGATGCAAGGGCTTTTTC AGGAGGGCCATGAAACGCAACGCCCGGCTGAGGTGCCCCTTCCGGAAGGGCGCCTGCGAGATCACCCGGAAGACC CGGCGACAGTGCCAGGCCTGCCGCCTGCGCAAGTGCCTGGAGAGCGGCATGAAGAAGGAGATGATCATGTCCGAC GAGGCCGTGGAGGAGAGGCGGGCCTTGATCAAGCGGAAGAAAAGTGAACGGACAGGGACTCAGCCACTGGGAGTG CAGGGGCTGACAGAGGAGCAGCGGATGATGATCAGGGAGCTGATGGACGCTCAGATGAAAACCTTTGACACTACC TTCTCCCATTTCAAGAATTTCCGGCTGCCAGGGGTGCTTAGCAGTGGCTGCGAGTTGCCAGAGTCTCTGCAGGCC CCATCGAGGGAAGAAGCTGCCAAGTGGAGCCAGGTCCGGAAAGATCTGTGCTCTTTGAAGGTCTCTCTGCAGCTG CGGGGGGAGGATGGCAGTGTCTGGAACTACAAACCCCCAGCCGACAGTGGCGGGAAAGAGATCTTCTCCCTGCTG CCCCACATGGCTGACATGTCAACCTACATGTTCAAAGGCATCATCAGCTTTGCCAAAGTCATCTCCTACTTCAGG GACTTGCCCATCGAGGACCAGATCTCCCTGCTGAAGGGGGCCGCTTTCGAGCTGTGTCAACTGAGATTCAACACA GTGTTCAACGCGGAGACTGGAACCTGGGAGTGTGGCCGGCTGTCCTACTGCTTGGAAGACACTGCAGGTGGCTTC CAGCAACTTCTACTGGAGCCCATGCTGAAATTCCACTACATGCTGAAGAAGCTGCAGCTGCATGAGGAGGAGTAT GTGCTGATGCAGGCCATCTCCCTCTTCTCCCCAGACCGCCCAGGTGTGCTGCAGCACCGCGTGGTGGACCAGCTG CAGGAGCAATTCGCCATTACTCTGAAGTCCTACATTGAATGCAATCGGCCCCAGCCTGCTCATAGGTTCTTGTTC CTGAAGATCATGGCTATGCTCACCGAGCTCCGCAGCATCAATGCTCAGCACACCCAGCGGCTGCTGCGCATCCAG GACATACACCCCTTTGCTACGCCCCTCATGCAGGAGTTGTTCGGCATCACAGGTAGCGGTGGCTCTGGTGGCTCC GGTGGTTCTTCTCATAGCTCATTGACAGAACGGCATAAAATTCTACACCGGCTCTTACAGGAGGGTAGCCCCTCA TAA

In an embodiment of the present invention, a “fusion” of PXR is PXR_(full)-L8-SRC, PXR_(full)-L10-SRC, PXR_(full)-L13-SRC, PXR-LBD-L8-SRC, PXR-LBD-L10-SRC or PXR-LBD-L13-SRC. Embodiments of the present invention also include a PXR “fusion” comprising PXR_(full)-L8-SRC, PXR_(full)-L10-SRC, PXR_(full)-L13-SRC, PXR-LBD-L8-SRC, PXR-LBD-L10-SRC or PXR-LBD-L13-SRC but excluding the N-terminal MKKGHHHHHH (SEQ ID NO: 34) sequence.

Example 3 Bacterial Expression and Purification

Ampicillin-resistant colonies of E. coli BL21(DE3) cells transformed with expression plasmid DNA were streaked out on a fresh Luria-Bertani (LB) agar plate containing 100 μg/ml ampicillin and were grown overnight at 37° C. A single isolated colony was placed into LB and grown at 37° C. to near saturation. Sterile glycerol was added to this culture to a final concentration of 15% and aliquots were stored at −80° C. These frozen samples were used as innoculum for further expression experiments. For expression, 2 L cells were grown to an OD600=3-4 in Terrific Broth (TB) containing 100 μg/ml ampicillin at 37° C. Induction of the T7 promoter was initiated by adding 0.2 mM isopropyl β-D-thiogalactopyranoside (IPTG). The cells were shifted to 16° C. and rigorously shaken for 16 h, pelleted, and resuspended in 100 ml lysis buffer (25 mM Hepes, pH7.9, 5% Glycerol v/v, 150 mM NaCl, 1 mM DTT, 10 mM Imidazole). Twenty tablets of EDTA-free protease Inhibitors cocktail (Roche Diagnostic, Indianapolis, Ind.) and 5000 units/L benzonase (Sigma, St. Louis, Mo.) were added per liter of lysis buffer. The mixture was homogenized with a Dounce tissue homogenizer (Bellcoglass, NJ) and cells were subsequently disrupted by two passes through a Microfluidizer (Model M-110F, Microfluidics, MA) operated at 10,000 psi. The lysate was clarified by centrifugation at 85,000×g for 60 min. The supernatant was applied to a 5 ml Ni-NTA (Qiagen) column in the presence of 10 mM imidazole using a gradifrac system (Amersham Pharmacia, NJ). The column was washed with 15-20 column volumes (CVs) of lysis buffer. The bound PXR proteins were eluted with 7-10 CVs of lysis buffer supplemented with 250 mM imidazole.

The pooled fraction was applied to 10 ml of Q-Sepharose Fast Flow (Amersham Pharmacia, NJ) column equilibrated with buffer A (25 mM Hepes, pH7.9, 5% Glycerol v/v, 150 mM NaCl, 5 mM DTT). The flow-through was collected, concentrated to 10-20 mg/ml and applied to a Superdex 200 (Amersham Pharmacia, NJ) column pre-equilibrated with buffer A. Fractions containing greater than 95% pure recombinant PXR proteins, as judged by SDS-PAGE, were pooled, and frozen in liquid nitrogen prior to storage at −80° C.

Example 4 Stabilization of PXR-LBD with SRC-1 Peptide (Untethered) and/or SR12813

This example shows that PXR is stabilized by the presence of SRC1 and/or SR12813. PXR and SRC-1 peptide was produced using either a coexpression system or using the bicistronic PXR-RBS-SRC system. Expression of the polypeptides was confirmed by SDS-PAGE analysis.

Temperature-dependent protein denaturation of PXR alone or in combination with SRC-1 peptide (676-CPSSHSSLTERHKILHRLLQEGSPS-700) (SEQ ID NO: 36) and/or SR12813 was monitored by circular dichroism.

SRC-1 peptide contains an LXXLL motif which adopts an α-helical conformation and binds to the surface of the LBD, forming a “charge clamp” as seen in other NR-coactivator complexes (Gampe et al. 2000) (Nolte et al. 1998) (Xu et al. 2001) (Darimont et al. 1998), therefore reducing the “breathing” of the receptor and freezing the ligand in the active orientation.

The following structural formula represents SR12813:

CD spectra were recorded in the wavelength range 200-300 nm in buffer A at 296 K on a Jasco J-810 spectrapolarimeter. Spectra were acquired at a protein concentration of 2.5 μM using a 1 mm cuvette with a slit width set to 2 nm and a response time of 1 second.

CD-monitored thermal denaturation was carried out in buffer A. Thermal scans were performed in a 1 mm cuvette, following the ellipticity at 220 nm using a response time of 4 seconds. A PTC-424S six position automatic Peltier accessory allowed continuous monitoring of the thermal transition at a constant rate of 2° C./min. The data were analyzed using the JASCO software assuming a two-state reversible equilibrium transition as described earlier (Buczek et al., Protein Sci. 11: 924-932 (2002)).

The results of the temperature-dependent circular dichroism analysis are set forth below in Table 1.

TABLE 1 Stabilization data Tm (C.) ΔTm (C.) Kd (M) reported Kd (M) apo PXR 41.5 +50 uM SRC-1 45.5 4.0 1.34E−06 +50 uM SR 12813 53.2 11.7 1.46E−08 4.1E−08 +50 uM SRC 56.4 14.9 +50 uM SR12813

Example 5 Stabilization of PXR-LBD-L10-SRC

This example shows that PXR-LBD fused to a SRC peptide is further stabilized by the presence of any of several other binding compounds. PXR-LBD-L10-SRC was expressed and purified essentially as set forth above. Expression was confirmed by SDS-PAGE analysis. Stabilization of PXR-LBD-L10-SRC in the presence of various substances was measured by temperature-dependent circular dichroism. PXR-LBD-L10-SRC was assayed under the following conditions:

-   Buffer: 25 mM Hepes, pH 7.9, 150 mM NaCl, 5% glycerol, 10 mM BME, -   wavelength: 225 nm -   heating ramp at 2° C./min -   temperature range: 30-80° C. -   protein concentration: 2.5 μM -   compound concentration: 25 μM

The results of the temperature-dependent circular dichroism analysis are set forth below in Table 2.

TABLE 2 Stabilization data Tm ΔTm Kd reported PXR-LBD-L10-SRC (C) (C) (M) Kd (M) (a) PXR-LBD-L10-SRC apo enzyme 52.9 ± 0.05 +25 uM SR 12813 60.5 7.6 6.7E-08 4E-08 +25 uM Hyperforin 59.7 6.8 1.0E-07 2E-07

+25 uM Clotrimazole 58.5 5.6 2.0E- 07 3E-07

+25 uM ritonavir 57.1 4.2 4.5E-07 1E-07

+25 uM sulfopyrole 55.2 2.3 1.3E-06 3E-07

(b) 1 uM PXR-LBD-L10- 55.3 SRC +10 uM pregnane-16α- 53.5 NA NA carbonitrile (PCN)

Example 7 Ligand Binding Assay

A total of 3 ug purified human PXR-LBD-L10-SRC (SEQ ID NO: 24) in PBS was incubated with serial dilutions of [³H]-SR12813 or [³H]-clotrimazole in a 96-well microtiter plate. After one hour of incubation at room temperature, the mixture was transferred to an imobilon multiScreen filter plate (Millipore). The plate was washed five times with PBS and dried under vacuum. The dried plate was added Opti-Fluor Scitillation cocktail before counting in a Parkard Top-counter.

TABLE 3 SR12813 binding [³H]-SR12813 concentration (nM) +PXR (CPM) −PXR (CPM) 2000 12990 2462 600 2535 592 200 113 175 60 330 98 20 126 50 6 98 59

TABLE 4 Clotrimazole binding [³H]clotrimazole concentration (nM) +PXR (CPM) −PXR (CPM) 300 9128 5335 100 2981 2373 30 1131 860 10 406 379 3 269 229 1 111 81

These data demonstrate that PXR exhibits significant SR12813 and clotrimazole binding activity.

Example 8 Reporter Gene Assay

HepG2 cells (American Type Culture Collection) were plated in 48-well plates in 250 μL of Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum and antibiotics and incubated overnight. In each well, 250 ng of pGL3-3A4 (Goodwin et al., Mol Pharmacol 56(6):1329-1339 (1999)), 40 ng of expression vector pcDNA4-hPXR (Kliewer et al., Cell 92:73-82 (1998)) and 20 ng of pRLTK (Promega) were transfected by mixing with 0.9 μL of Fugene 6 (Roche Applied Sciences) and 30 μL of DMEM serum-free medium. Six hours after transfection, the medium was replaced with DMEM containing different concentrations of test articles, and incubated for 44 hours. The cells were lysed, subjected to one freeze-thaw cycle and analyzed for luciferase activities using Promega's Dual Luciferase Assay kit. A luciferase index was calculated based on the ratio of the firefly luciferase activity and the Renilla luciferase activity. The fold of induction by the test compound was calculated based on the luciferase index from cells treated with DMSO.

The data presented in Table 5 shows that the PXR reporter-gene system has a good predictability for CYP3A4 induction liability, and can be used as a valuable screening tool in eliminating potent CYP3A4 inducers in the early stage of drug development process.

TABLE 5 Human PXR reporter gene activity after treated with rifampicin and RU486 (inducers) and pregnan-16-carbonitrile (non-inducer) rifampicin pregnan-16- concentration (fold of carbonitrile RU486 (uM) induction) (fold of induction) (fold of induction) 1 45 6 12 3 50 5 26 10 60 5 42 30 55 7 36

Example 9 Crystallography

Crystals of PXR-LBD-linker-SRC (where the linker can be 8, 10, or 13 amino acids long) were grown using the hanging-drop vapor diffusion method in which 1 μl of protein (10 mg/ml) in buffer GF was mixed with an equal volume of precipitant, placed on the underside of a siliconized glass coverslip and sealed in close proximity to 1 ml of the precipitant solution. The precipitant solution contained 2,4-methylpentanediol (MPD) as well as 100 mM imidazole/HCl buffer titrated to pH 8.0. The crystallization experiment was performed using MPD concentrations ranging from 10% v/v to 30% v/v. Crystals appeared as soon as 1 day after incubating at 4° C. and grew to a final size of 0.2×0.3×0.4 mm after approximately one week. Crystals of PXR-linker-SRC could also be grown using isopropanol as a precipitant or buffered using MES titrated to pH 7.1 or with incubation at 18° C.

Photomicrographic analysis confirmed the generation of PXR-L10-SRC crystals. The crystal of PXR-L10-SRC apoprotein was grown from 16% (v/v) isopropanol, 50 mM MES pH 7.1.

Example 10 Crystallographic Analysis of PXR-LBD-L10-SRC

Crystals of human PXR-LBD-L10-SRC (SEQ ID NO: 24) were flash-cooled in liquid nitrogen (LN2) directly from the crystallization drop or alternatively soaked in an artificial mother liquor containing 30% (v/v) MPD and 100 mM imidazole/HCl titrated to pH 8.0. The artificial mother liquor can contain up to 12% (v/v) DMSO and may also contain a molecule which binds to PXR-LBD-L10-SRC at a suitably high concentration, such as 4 mM.

Diffraction data were collected using a Rigaku R-AXIS HTC detector mounted on a Rigaku FR-E SuperBright X-ray generator equipped with VariMax HF X-ray focusing optics. Data were collected, indexed, integrated, scaled, and reduced using the program CrystalClear 1.3.6 (Rigaku/MSC). Two different crystal forms were observed. Crystallographic coordinates, data collection and reduction statistics are set forth below.

crystal 1 Data collection statistics: Resolution 100-2.3 Å No. of collected reflections 143193 No. of unique reflections (F >= 0) 36357 R-sym 0.096 Percent of theoretical (I/s >= 1) 99.0% Unit Cell a = 84.2 Å, b = 90.0 Å, c = 106.6 Å, α = β = γ = 90° Space Group P2₁2₁2₁ Asymmetric unit 2 molecules crystal 2 Data collection statistics: Resolution 100-2.2 Å No. of collected reflections 205346 No. of unique reflections (F >= 0) 20724 R-sym 0.066 Percent of theoretical (I/s >= 1) 99.8% Unit Cell a = b = 94.2 Å, c = 88.2 Å, α = β = γ = 90° Space Group P4₃2₁2 Asymmetric unit 1 molecule

The initial crystal structures of PXR-LBD-L10-SRC apoprotein in each of the observed space groups was solved by molecular replacement using the program MOLREP (CCP4). The probe was derived from PDB code 1NRL in which only one chain of PXR-LBD was used, and it was stripped of all solvent and ligand molecules. Rigid-body refinement was followed by iterative positional and B-factor refinement with automated addition of solvent molecules using the software AutoBUSTER (GPL). Using the refined apoprotein coordinates, the ligand-bound form was solved by applying rigid-body refinement followed by iterative positional and B-factor refinement with automated addition of solvent molecules using the software AutoBUSTER (Global Phasing Limited, Inc.).

crystal 1 Theoretical number of reflections 37217 Number of reflections in working set 34471 (92.6%) Number of reflections in test set 1828 (4.9%) Number of refined atoms (total) 4853 Number of solvent atoms 84 R-factor 0.240 R-free 0.291 RMSD bond length 0.011 Å RMSD bond angles 1.3°

TABLE 3a Crystal coordinates for crystal 1 The following table contains one line for each atom in the first of the two observed PXR-LBD-L10-SRC monomers in the orthorhombic asymmetric unit. The columns are: 1) residue number, 2) 1-letter amino acid code, 3) atom name, 4) x-coordinate multiplied by 10, 5) y-coordinate multiplied by 10, 6) z-coordinate multiplied by 10, and 7) B-factor. 142 G N 22 197 596 64 142 G CA 28 187 588 63 142 G C 19 183 576 65 142 G O 7 185 576 64 143 L N 25 178 566 62 143 L CA 17 174 554 59 143 L C 12 160 555 64 143 L O 19 151 560 66 143 L CB 26 175 541 58 143 L CG 28 189 535 58 143 L CD1 42 190 530 57 143 L CD2 18 192 525 55 144 T N 1 157 548 59 144 T CA −4 143 549 59 144 T C 5 135 541 67 144 T O 12 139 532 68 144 T CB −18 142 543 65 144 T OG1 −17 136 530 65 144 T CG2 −24 155 541 63 145 E N 5 122 543 66 145 E CA 13 112 536 65 145 E C 10 112 521 65 145 E O 18 109 513 65 145 E CB 9 98 542 66 145 E CG 14 86 533 82 145 E CD 30 85 534 6 145 E OE1 34 73 532 23 145 E OE2 36 95 537 89 146 E N −2 116 517 61 146 E CA −5 116 503 61 146 E C 0 129 496 65 146 E O 2 129 484 67 146 E CB −21 116 501 62 146 E CG −25 106 490 78 146 E CD −23 92 493 12 146 E OE1 −32 86 500 12 146 E OE2 −12 86 490 13 147 Q N 3 139 504 57 147 Q CA 8 151 498 54 147 Q C 23 151 498 56 147 Q O 30 157 490 57 147 Q CB 4 163 507 55 147 Q CG −11 164 508 68 147 Q CD −15 174 519 66 147 Q OE1 −9 176 529 61 147 Q NE2 −26 181 515 58 148 R N 29 143 508 49 148 R CA 43 141 508 49 148 R C 47 132 496 55 148 R O 57 135 489 55 148 R CB 47 135 521 49 148 R CG 51 145 531 63 148 R CD 58 139 544 87 148 R NE 48 131 551 11 148 R CZ 48 129 564 33 148 R NH1 57 135 572 24 148 R NH2 38 122 570 22 149 M N 39 123 492 53 149 M CA 42 114 481 55 149 M C 40 121 468 56 149 M O 46 119 458 56 149 M CB 33 102 481 59 149 M CG 33 94 494 65 149 M SD 49 87 498 72 149 M CE 54 80 481 68 150 M N 29 130 468 51 150 M CA 25 137 456 49 150 M C 37 146 452 46 150 M O 39 149 440 43 150 M CB 14 146 460 51 150 M CG 11 157 450 54 150 M SD −6 163 451 57 150 M CE −16 149 445 50 151 I N 44 152 462 42 151 I CA 56 161 459 42 151 I C 68 152 455 49 151 I O 75 156 446 52 151 I CB 59 169 471 43 151 I CG1 47 179 474 43 151 I CG2 71 177 469 42 151 I CD1 46 184 488 45 152 R N 70 141 462 45 152 R CA 81 132 459 45 152 R C 80 129 444 46 152 R O 90 129 438 45 152 R CB 80 119 467 47 152 R CG 92 110 465 69 152 R CD 106 118 464 86 152 R NE 117 109 466 92 152 R CZ 124 107 478 97 152 R NH1 121 114 489 77 152 R NH2 134 99 478 85 153 E N 68 126 440 40 153 E CA 66 122 426 39 153 E C 70 133 416 45 153 E O 76 131 406 46 153 E CB 52 117 423 39 153 E CG 53 105 414 55 153 E CD 43 104 403 77 153 E OE1 31 108 406 58 153 E OE2 45 98 392 77 154 L N 66 146 419 40 154 L CA 68 158 411 37 154 L C 84 160 411 39 154 L O 89 162 401 38 154 L CB 61 170 417 36 154 L CG 48 175 411 41 154 L CD1 42 166 401 40 154 L CD2 37 178 422 44 155 M N 90 160 423 35 155 M CA 105 162 425 32 155 M C 113 151 418 38 155 M O 123 154 412 41 155 M CB 108 162 440 34 155 M CG 103 174 448 36 155 M SD 109 190 440 40 155 M CE 124 192 449 38 156 D N 108 139 418 36 156 D CA 115 128 411 37 156 D C 114 131 396 38 156 D O 124 131 389 38 156 D CB 107 115 414 43 156 D CG 113 103 407 68 156 D OD1 107 97 398 69 156 D OD2 125 100 411 78 157 A N 102 134 391 35 157 A CA 100 137 377 35 157 A C 109 148 373 37 157 A O 115 148 362 35 157 A CB 86 141 375 37 158 Q N 110 159 381 36 158 Q CA 118 171 377 35 158 Q C 132 167 377 37 158 Q O 140 172 369 41 158 Q CB 115 181 388 36 158 Q CG 123 194 387 40 158 Q CD 116 205 378 46 158 Q OE1 110 202 368 42 158 Q NE2 118 217 382 31 159 M N 137 159 387 34 159 M CA 151 156 387 36 159 M C 155 148 376 37 159 M O 166 150 371 34 159 M CB 156 150 401 39 159 M CG 155 135 401 44 159 M SD 170 126 396 48 159 M CE 161 111 399 45 160 K N 147 138 372 35 160 K CA 150 130 361 34 160 K C 149 137 347 44 160 K O 153 132 338 46 160 K CB 140 118 360 34 160 K CG 141 108 371 43 160 K CD 127 102 374 52 160 K CE 127 87 377 63 160 K NZ 135 83 390 57 161 T N 142 149 347 42 161 T CA 140 155 334 40 161 T C 144 170 332 43 161 T O 141 175 321 43 161 T CB 125 155 331 48 161 T OG1 118 163 341 46 161 T CG2 119 141 331 47 162 F N 151 175 341 42 162 F CA 155 190 340 41 162 F C 170 190 340 49 162 F O 176 189 350 49 162 F CB 150 198 352 41 162 F CG 152 213 351 40 162 F CD1 149 221 361 40 162 F CD2 158 218 339 43 162 F CE1 152 235 360 41 162 F CE2 160 231 338 43 162 F CZ 157 240 348 41 163 D N 175 193 328 48 163 D CA 190 193 327 47 163 D C 195 207 331 49 163 D O 198 216 323 49 163 D CB 195 191 312 48 163 D CG 210 191 311 51 163 D OD1 218 188 320 45 163 D OD2 214 191 299 56 164 T N 194 209 344 43 164 T CA 198 222 350 42 164 T C 211 229 345 48 164 T O 211 241 343 51 164 T CB 197 222 365 37 164 T OG1 207 213 370 39 164 T CG2 184 217 370 32 165 T N 221 221 341 41 165 T CA 233 226 336 40 165 T C 233 226 320 47 165 T O 244 229 315 50 165 T CB 245 218 341 41 165 T OG1 244 205 337 45 165 T CG2 246 220 356 35 166 F N 223 222 314 42 166 F CA 222 221 299 41 166 F C 234 214 293 47 166 F O 238 217 282 49 166 F CB 220 234 292 41 166 F CG 208 242 297 41 166 F CD1 199 246 288 41 166 F CD2 208 246 310 41 166 F CE1 188 253 293 40 166 F CE2 197 253 315 42 166 F CZ 187 256 306 39 167 S N 239 203 299 44 167 S CA 250 195 295 45 167 S C 246 188 282 53 167 S O 255 184 275 54 167 S CB 254 185 305 51 167 S OG 242 179 310 65 168 H N 234 185 280 54 168 H CA 229 177 269 56 168 H C 224 185 257 56 168 H O 220 180 247 57 168 H CB 219 167 273 59 168 H CG 225 156 282 65 168 H ND1 230 159 295 69 168 H CD2 228 143 280 68 168 H CE1 235 148 300 68 168 H NE2 234 138 291 69 169 F N 224 199 259 49 169 F CA 221 207 248 46 169 F C 233 209 239 50 169 F O 243 216 243 46 169 F CB 217 221 253 46 169 F CG 210 230 243 44 169 F CD1 201 225 234 46 169 F CD2 213 243 243 41 169 F CE1 196 233 224 45 169 F CE2 207 252 234 41 169 F CZ 198 247 225 40 170 K N 233 204 227 50 170 K CA 244 206 218 50 170 K C 239 205 204 54 170 K O 227 204 201 52 170 K CB 255 197 221 52 170 K CG 252 186 231 65 170 K CD 251 172 223 80 170 K CE 239 164 229 8 170 K NZ 227 165 220 21 171 N N 248 207 194 54 171 N CA 245 207 180 55 171 N C 234 217 176 59 171 N O 227 214 166 62 171 N CB 240 192 176 57 171 N CG 251 182 179 93 171 N OD1 248 170 178 94 171 N ND2 262 186 184 78 172 F N 234 228 183 52 172 F CA 223 238 180 50 172 F C 228 249 171 52 172 F O 240 253 171 54 172 F CB 219 244 193 50 172 F CG 230 248 202 49 172 F CD1 236 261 201 49 172 F CD2 235 239 212 50 172 F CE1 246 265 209 48 172 F CE2 245 243 220 51 172 F CZ 251 256 219 48 173 R N 220 254 162 46 173 R CA 224 265 153 44 173 R C 228 277 160 48 173 R O 222 280 171 48 173 R CB 213 268 143 37 173 R CG 209 255 135 40 173 R CD 196 258 127 39 173 R NE 184 254 135 56 173 R CZ 172 258 131 67 173 R NH1 171 265 119 53 173 R NH2 161 254 137 60 174 L N 235 286 154 46 174 L CA 240 299 160 47 174 L C 239 309 148 57 174 L O 240 306 136 57 174 L CB 254 298 164 47 174 L CG 259 294 179 52 174 L CD1 274 293 180 50 174 L CD2 253 303 190 50 175 P N 237 322 152 56 175 P CA 237 333 142 55 175 P C 250 333 134 64 175 P O 261 335 140 64 175 P CB 236 345 151 56 175 P CG 236 341 165 60 175 P CD 240 327 166 56 176 G N 249 330 121 62 176 G CA 260 329 113 63 176 G C 269 341 114 66 176 G O 265 352 118 65 177 V N 282 340 111 62 177 V CA 292 351 112 62 177 V C 294 356 97 72 177 V O 292 368 95 74 177 V CB 305 345 117 65 177 V CG1 306 330 115 64 177 V CG2 316 352 111 64 192 S N 15 438 −11 70 192 S CA 24 447 −4 71 192 S C 17 455 8 79 192 S O 23 455 19 79 192 S CB 32 457 −13 75 192 S OG 41 464 −5 83 193 R N 6 461 5 77 193 R CA −2 468 16 78 193 R C −4 458 28 84 193 R O −2 462 39 83 193 R CB −15 473 10 82 193 R CG −24 480 22 100 193 R CD −22 495 22 16 193 R NE −19 500 35 25 193 R CZ −17 513 38 37 193 R NH1 −14 517 50 27 193 R NH2 −18 522 28 15 194 E N −9 446 24 82 194 E CA −12 437 35 81 194 E C 1 431 41 85 194 E O 2 430 53 85 194 E CB −21 425 29 83 194 E CG −29 417 39 98 194 E CD −24 402 40 34 194 E OE1 −12 400 37 30 194 E OE2 −32 394 44 36 195 E N 11 430 32 80 195 E CA 24 425 36 78 195 E C 32 435 44 83 195 E O 41 431 52 82 195 E CB 32 421 23 79 195 E CG 26 408 17 90 195 E CD 25 396 26 6 195 E OE1 13 391 28 5 195 E OE2 35 393 33 90 196 A N 28 448 43 81 196 A CA 35 459 50 81 196 A C 31 459 65 83 196 A O 40 460 74 83 196 A CB 31 472 44 82 197 A N 18 458 67 78 197 A CA 12 459 81 78 197 A C 15 445 88 81 197 A O 11 444 100 80 197 A CB −3 461 80 78 198 K N 20 436 81 77 198 K CA 24 423 86 76 198 K C 38 424 92 77 198 K O 40 424 104 78 198 K CB 24 412 76 77 198 K CG 11 404 75 76 198 K CD 13 390 68 84 198 K CE 1 382 67 100 198 K NZ 3 370 59 15 199 W N 47 427 83 70 199 W CA 61 429 87 69 199 W C 63 440 98 74 199 W O 73 441 104 75 199 W CB 69 433 75 67 199 W CG 72 422 65 67 199 W CD1 63 416 57 70 199 W CD2 85 416 63 66 199 W NE1 69 407 49 68 199 W CE2 82 406 53 69 199 W CE3 97 417 68 67 199 W CZ2 92 398 48 68 199 W CZ3 107 409 64 68 199 W CH2 105 399 53 69 200 S N 53 450 98 71 200 S CA 54 461 108 70 200 S C 52 456 122 70 200 S O 58 462 131 70 200 S CB 43 472 104 74 200 S OG 34 473 115 75 201 Q N 43 447 123 65 201 Q CA 39 441 137 64 201 Q C 51 432 141 68 201 Q O 56 433 152 66 201 Q CB 27 433 136 65 201 Q CG 21 429 149 69 201 Q CD 17 441 156 81 201 Q OE1 22 443 168 79 201 Q NE2 8 449 151 64 202 V N 55 424 131 65 202 V CA 67 415 133 66 202 V C 80 421 138 73 202 V O 87 416 146 73 202 V CB 68 406 120 69 202 V CG1 82 399 121 69 202 V CG2 57 395 120 69 203 R N 82 434 133 71 203 R CA 94 442 137 71 203 R C 93 445 152 74 203 R O 103 444 159 75 203 R CB 94 455 130 71 203 R CG 94 454 115 85 203 R CD 100 467 109 7 203 R NE 101 467 94 29 203 R CZ 94 475 86 49 203 R NH1 86 484 91 33 203 R NH2 95 474 73 40 204 K N 82 449 157 70 204 K CA 80 452 171 70 204 K C 81 440 179 76 204 K O 88 440 190 76 204 K CB 66 458 172 72 204 K CG 63 469 162 83 204 K CD 50 476 165 89 204 K CE 46 485 153 88 204 K NZ 33 493 155 81 205 D N 75 429 175 71 205 D CA 74 417 182 71 205 D C 88 413 188 76 205 D O 89 412 201 76 205 D CB 69 405 173 71 205 D CG 54 406 171 75 205 D OD1 46 411 180 78 205 D OD2 49 401 161 72 206 L N 98 412 180 72 206 L CA 112 408 185 72 206 L C 121 420 187 81 206 L O 133 419 182 82 206 L CB 117 399 175 71 206 L CG 116 402 160 74 206 L CD1 125 413 156 74 206 L CD2 117 390 151 76 207 C N 117 430 194 82 207 C CA 127 442 196 83 207 C C 129 444 210 88 207 C O 138 451 214 88 207 C CB 122 454 189 83 207 C SG 105 461 194 87 208 S N 119 439 218 84 208 S CA 119 442 233 84 208 S C 125 430 241 88 208 S O 132 433 251 89 208 S CB 104 444 237 86 208 S OG 96 439 228 96 209 L N 122 418 236 84 209 L CA 128 406 242 82 209 L C 141 403 236 84 209 L O 144 392 232 84 209 L CB 118 395 240 82 209 L CG 104 397 247 87 209 L CD1 93 401 237 88 209 L CD2 99 384 255 88 210 K N 149 413 234 76 210 K CA 162 412 227 74 210 K C 173 408 236 75 210 K O 175 414 247 76 210 K CB 165 425 220 76 210 K CG 164 425 204 81 210 K CD 168 438 198 88 210 K CE 181 437 191 83 210 K NZ 187 451 189 91 211 V N 180 397 232 66 211 V CA 191 392 241 64 211 V C 204 392 233 64 211 V O 205 390 221 63 211 V CB 188 378 246 67 211 V CG1 182 379 260 66 211 V CG2 180 370 236 66 212 S N 215 391 242 59 212 S CA 228 389 237 58 212 S C 232 375 242 61 212 S O 225 369 250 61 212 S CB 238 399 244 59 212 S OG 247 392 252 70 213 L N 243 369 236 56 213 L CA 246 355 238 56 213 L C 260 352 242 60 213 L O 269 356 235 62 213 L CB 242 348 225 57 213 L CG 242 333 225 63 213 L CD1 233 329 213 64 213 L CD2 256 328 222 70 214 Q N 262 345 253 56 214 Q CA 276 342 257 55 214 Q C 278 327 255 60 214 Q O 268 319 256 62 214 Q CB 279 345 272 56 214 O CG 293 343 275 65 214 Q CD 298 351 287 75 214 Q OE1 299 363 286 74 214 Q NE2 302 344 297 49 215 L N 290 323 253 57 215 L CA 292 309 251 58 215 L C 306 305 257 63 215 L O 316 307 251 65 215 L CB 292 306 236 58 215 L CG 281 299 229 61 215 L CD1 284 284 227 61 215 L CD2 268 300 236 64 216 R N 306 301 270 57 216 R CA 319 298 276 56 216 R C 324 284 273 63 216 R O 319 274 278 65 216 R CB 319 300 291 53 216 R CG 316 314 295 68 216 R CD 312 315 309 72 216 R NE 300 308 312 61 216 R CZ 288 311 307 77 216 R NH1 287 321 299 47 216 R NH2 277 304 310 77 217 G N 335 283 265 58 217 G CA 340 270 261 58 217 G C 348 264 273 65 217 G O 353 271 281 63 218 E N 348 251 273 65 218 E CA 355 244 284 66 218 E C 370 248 286 73 218 E O 375 247 297 75 218 E CB 354 228 282 68 218 E CG 341 223 276 81 218 E CD 339 208 277 96 218 E OE1 337 202 266 81 218 E OE2 341 202 287 70 219 D N 376 254 275 68 219 D CA 390 258 276 66 219 D C 392 271 283 71 219 D O 403 273 289 73 219 D CB 396 260 262 66 219 D CG 387 268 252 72 219 D OD1 379 276 257 71 219 D OD2 389 267 240 76 220 G N 382 280 283 68 220 G CA 384 293 290 68 220 G C 379 304 280 70 220 G O 376 315 284 68 221 S N 379 300 267 65 221 S CA 375 309 256 63 221 S C 360 313 258 62 221 S O 352 306 263 61 221 S CB 376 301 243 67 221 S OG 365 294 239 77 222 V N 357 325 253 56 222 V CA 343 330 254 54 222 V C 339 337 241 57 222 V O 347 345 236 56 222 V CB 342 340 266 57 222 V CG1 327 346 267 55 222 V CG2 346 334 279 57 223 W N 328 333 236 53 223 W CA 322 339 223 53 223 W C 310 347 227 57 223 W O 303 343 236 56 223 W CB 318 327 214 52 223 W CG 328 323 204 54 223 W CD1 335 311 204 57 223 W CD2 332 330 192 53 223 W NE1 342 310 193 56 223 W CE2 341 321 185 58 223 W CE3 329 342 187 55 223 W CZ2 347 325 173 58 223 W CZ3 335 346 174 57 223 W CH2 343 337 168 57 224 N N 308 359 221 55 224 N CA 297 367 225 55 224 N C 290 373 213 59 224 N O 297 379 204 61 224 N CB 303 379 233 48 224 N CG 292 386 241 64 224 N OD1 286 395 235 71 224 N ND2 289 381 252 54 225 Y N 277 371 212 52 225 Y CA 270 376 201 51 225 Y C 261 387 206 58 225 Y O 253 385 214 57 225 Y CB 261 365 196 51 225 Y CG 252 369 184 52 225 Y CD1 257 370 171 54 225 Y CD2 239 373 186 51 225 Y CE1 250 374 161 56 225 Y CE2 231 377 176 52 225 Y CZ 236 378 163 61 225 Y OH 229 382 152 63 226 K N 262 399 199 55 226 K CA 254 410 202 55 226 K C 245 411 190 60 226 K O 250 412 179 59 226 K CB 263 423 203 59 226 K CG 256 434 211 75 226 K CD 267 441 220 84 226 K CE 264 455 223 94 226 K NZ 274 461 233 99 227 P N 232 411 192 55 227 P CA 223 412 181 54 227 P C 224 426 174 59 227 P O 231 435 179 58 227 P CB 209 410 187 55 227 P CG 211 416 201 60 227 P CD 225 412 205 55 228 P N 217 428 163 58 228 P CA 218 440 155 59 228 P C 209 450 162 72 228 P O 201 447 171 74 228 P CB 213 437 142 60 228 P CG 205 424 143 62 228 P CD 211 417 155 57 229 A N 209 463 157 72 229 A CA 199 473 161 72 229 A C 190 475 149 79 229 A O 194 480 139 78 229 A CB 206 486 165 72 230 D N 178 468 150 78 230 D CA 167 467 140 78 230 D C 169 477 128 88 230 D O 169 489 130 89 230 D CB 154 468 147 80 230 D CG 142 470 136 91 230 D OD1 144 465 125 92 230 D OD2 132 476 140 92 231 S N 170 471 116 85 231 S CA 172 479 104 84 231 S C 162 474 93 87 231 S O 153 465 96 86 231 S CB 186 478 99 88 231 S OG 189 488 90 0 232 G N 164 478 81 84 232 G CA 156 475 69 84 232 G C 146 463 70 87 232 G O 135 464 65 87 233 G N 151 452 76 82 233 G CA 143 440 77 82 233 G C 150 428 81 87 233 G O 155 427 93 87 234 K N 150 417 73 82 234 K CA 155 404 76 82 234 K C 164 402 89 86 234 K O 159 395 98 86 234 K CB 161 397 64 83 234 K CG 151 393 53 95 234 K CD 141 383 59 6 234 K CE 129 380 49 13 234 K NZ 118 371 54 10 235 E N 176 406 88 81 235 E CA 186 405 99 79 235 E C 181 403 114 82 235 E O 188 400 123 82 235 E CB 195 417 99 80 235 E CG 187 430 103 84 235 E CD 182 438 91 2 235 E OE1 186 435 79 80 235 E OE2 174 447 93 96 236 I N 168 407 116 75 236 I CA 162 407 129 73 236 I C 157 392 132 72 236 I O 152 389 143 73 236 I CB 151 417 130 75 236 I CG1 140 414 120 76 236 I CG2 156 431 129 76 236 I CD1 134 426 113 75 237 F N 160 383 122 64 237 F CA 156 370 123 61 237 F C 168 361 126 61 237 F O 167 348 125 60 237 F CB 150 366 109 63 237 F CG 137 374 106 66 237 F CD1 135 379 93 70 237 F CD2 127 375 116 70 237 F CE1 123 385 90 72 237 F CE2 115 382 113 74 237 F CZ 113 387 100 72 238 S N 179 366 129 55 238 S CA 192 359 130 55 238 S C 193 349 143 56 238 S O 201 341 142 55 238 S CB 203 368 130 59 238 S OG 204 375 143 75 239 L N 186 352 153 49 239 L CA 186 344 166 49 239 L C 174 334 166 55 239 L O 175 324 174 55 239 L CB 184 353 178 50 239 L CG 196 354 189 55 239 L CD1 208 348 183 56 239 L CD2 198 369 193 57 240 L N 164 336 158 51 240 L CA 152 327 158 49 240 L C 156 312 157 53 240 L O 151 303 164 55 240 L CB 143 331 146 48 240 L CG 135 344 149 51 240 L CD1 125 347 138 50 240 L CD2 128 344 162 50 241 P N 165 308 148 46 241 P CA 170 294 146 44 241 P C 175 288 159 50 241 P O 172 277 163 52 241 P CB 180 295 136 44 241 P CG 177 307 127 49 241 P CD 171 317 137 45 242 H N 184 296 166 46 242 H CA 190 291 179 46 242 H C 178 290 189 50 242 H O 177 279 195 49 242 H CB 199 302 184 47 242 H CG 206 298 197 51 242 H ND1 212 286 198 53 242 H CD2 206 304 209 53 242 H CE1 217 285 211 52 242 H NE2 213 296 217 53 243 M N 170 300 190 47 243 M CA 159 300 199 47 243 M C 150 288 197 48 243 M O 145 282 207 48 243 M CB 151 313 197 51 243 M CG 156 325 204 57 243 M SD 165 321 219 65 243 M CE 181 329 216 62 244 A N 148 284 185 42 244 A CA 140 272 181 38 244 A C 146 259 187 42 244 A O 138 251 192 43 244 A CB 139 272 166 38 245 D N 159 258 186 38 245 D CA 166 247 192 38 245 D C 166 247 207 46 245 D O 164 236 213 50 245 D CB 181 247 186 39 245 D CG 181 246 171 46 245 D OD1 171 242 165 42 245 D OD2 192 250 165 50 246 M N 167 258 213 37 246 M CA 166 259 227 36 246 M C 152 255 232 40 246 M O 151 248 242 41 246 M CB 170 273 233 38 246 M CG 167 273 248 41 246 M SD 177 261 257 44 246 M CE 191 270 263 40 247 S N 142 261 226 35 247 S CA 128 258 229 35 247 S C 124 244 227 41 247 S O 119 237 236 46 247 S CB 118 266 220 38 247 S OG 118 280 222 55 248 T N 128 238 216 37 248 T CA 126 224 212 35 248 T C 133 215 223 38 248 T O 126 205 227 41 248 T CB 132 221 199 43 248 T OG1 125 227 188 45 248 T CG2 131 206 196 39 249 Y N 145 219 227 32 249 Y CA 152 211 238 31 249 Y C 144 212 251 37 249 Y O 141 202 258 40 249 Y CB 166 216 240 33 249 Y CG 174 209 251 36 249 Y CD1 181 197 249 39 249 Y CD2 175 215 263 36 249 Y CE1 188 191 260 37 249 Y CE2 183 210 273 35 249 Y CZ 188 197 272 39 249 Y OH 195 191 282 51 250 M N 140 224 254 33 250 M CA 132 227 266 33 250 M C 118 220 266 41 250 M O 114 213 276 42 250 M CB 131 242 268 34 250 M CG 145 248 270 37 250 M SD 150 243 286 42 250 M CE 135 250 297 39 251 F N 111 221 255 38 251 F CA 98 214 253 39 251 F C 100 199 255 44 251 F O 91 192 260 45 251 F CB 92 216 239 41 251 F CG 87 229 236 43 251 F CD1 85 233 223 46 251 F CD2 83 238 246 41 251 F CE1 80 246 220 46 251 F CE2 78 250 244 44 251 F CZ 76 254 231 43 252 K N 110 193 249 41 252 K CA 112 178 250 43 252 K C 115 175 265 42 252 K O 111 165 270 46 252 K CB 124 173 242 46 252 K CG 124 177 228 51 252 K CD 135 170 220 60 252 K CE 135 155 222 77 252 K NZ 140 148 210 94 253 G N 121 184 272 39 253 G CA 124 183 286 39 253 G C 111 182 295 46 253 G O 110 175 305 48 254 I N 101 190 290 43 254 I CA 88 191 296 42 254 I C 79 179 293 44 254 I O 71 175 302 44 254 I CB 80 203 290 44 254 I CG1 87 216 293 43 254 I CG2 66 203 296 43 254 I CD1 87 219 308 38 255 I N 79 175 281 37 255 I CA 72 162 276 33 255 I C 77 151 285 37 255 I O 69 143 291 40 255 I CB 75 159 262 34 255 I CG1 72 170 252 34 255 I CG2 68 145 258 32 255 I CD1 70 166 238 36 256 S N 90 149 286 31 256 S CA 95 139 295 31 256 S C 90 140 309 36 256 S O 88 130 316 35 256 S CB 111 138 295 31 256 S OG 116 134 282 41 257 F N 89 152 315 30 257 F CA 85 154 328 29 257 F C 71 150 331 37 257 F O 68 141 339 39 257 F CB 85 170 330 30 257 F CG 79 174 343 30 257 F CD1 86 173 355 32 257 F CD2 67 182 343 30 257 F CE1 80 178 367 31 257 F CE2 62 186 354 33 257 F CZ 68 184 367 30 258 A N 61 154 323 33 258 A CA 47 151 323 34 258 A C 45 136 323 44 258 A O 39 130 332 46 258 A CB 41 157 310 33 259 K N 52 129 313 45 259 K CA 51 114 312 46 259 K C 55 106 324 51 259 K O 49 96 327 52 259 K CB 61 111 301 48 259 K CG 55 112 287 54 259 K CD 65 106 276 68 259 K CE 75 96 282 73 259 K NZ 87 94 274 87 260 V N 65 111 332 46 260 V CA 69 104 344 44 260 V C 59 105 356 51 260 V O 61 97 366 50 260 V CB 84 107 348 47 260 V CG1 91 113 337 45 260 V CG2 84 116 360 47 261 I N 49 112 354 50 261 I CA 39 115 365 49 261 I C 27 106 363 55 261 I O 19 107 353 56 261 I CB 34 130 364 51 261 I CG1 46 138 368 51 261 I CG2 22 132 374 50 261 I CD1 44 153 364 57 262 S N 24 97 373 50 262 S CA 13 88 372 50 262 S C 0 95 369 54 262 S O −8 91 360 54 262 S CB 11 80 385 51 262 S OG 16 87 396 58 263 Y N −3 106 376 50 263 Y CA −15 114 374 49 263 Y C −18 117 360 51 263 Y O −29 116 356 50 263 Y CB −14 127 383 50 263 Y CG −10 124 397 51 263 Y CD1 2 127 402 53 263 Y CD2 −20 119 406 53 263 Y CE1 6 124 415 55 263 Y CE2 −17 117 419 55 263 Y CZ −4 119 424 62 263 Y OH 0 116 437 62 264 F N −7 121 352 49 264 F CA −8 124 338 47 264 F C −9 112 328 53 264 F O −15 113 318 49 264 F CB 5 132 335 47 264 F CG 5 138 321 47 264 F CD1 0 150 319 49 264 F CD2 11 131 311 49 264 F CE1 0 156 306 49 264 F CE2 12 137 298 51 264 F CZ 6 149 296 49 265 R N −1 102 331 52 265 R CA −1 90 323 53 265 R C −15 84 322 59 265 R O −20 81 312 58 265 R CB 9 79 329 55 265 R CG 23 81 325 61 265 R CD 31 68 325 66 265 R NE 38 67 338 72 265 R CZ 32 63 349 95 265 R NH1 19 61 349 96 265 R NH2 38 62 361 80 266 D N −21 83 334 55 266 D CA −35 77 335 54 266 D C −45 84 326 60 266 D O −56 79 325 61 266 D CB −40 77 350 55 266 D CG −29 71 359 62 266 D OD1 −21 62 355 56 266 D OD2 −30 75 371 79 267 L N −42 96 322 56 267 L CA −51 104 313 55 267 L C −50 100 299 58 267 L O −39 97 294 57 267 L CB −48 119 314 54 267 L CG −50 128 326 60 267 L CD1 −46 142 323 60 267 L CD2 −65 127 331 64 268 P N −61 99 292 54 268 P CA −61 94 278 54 268 P C −51 103 270 63 268 P O −51 115 272 64 268 P CB −75 96 273 56 268 P CG −81 106 281 60 268 P CD −74 106 294 55 269 I N −44 96 261 61 269 I CA −34 103 252 60 269 I C −39 116 247 65 269 I O −31 126 246 65 269 I CB −30 94 240 62 269 I CG1 −18 99 233 64 269 I CG2 −41 96 229 62 269 I CD1 −5 97 241 74 270 E N −51 117 243 62 270 E CA −56 130 237 61 270 E CB −69 128 230 63 270 E C −55 141 246 64 270 E O −51 152 243 63 271 D N −59 139 259 59 271 D CA −58 149 270 58 271 D C −44 152 273 57 271 D O −41 163 276 59 271 D CB −65 143 282 61 271 D CG −80 144 282 79 271 D OD1 −87 138 290 81 271 D OD2 −85 151 272 88 272 Q N −35 142 272 46 272 Q CA −21 144 274 46 272 Q C −15 153 264 51 272 Q O −6 162 266 52 272 Q CB −14 130 273 46 272 Q CG −16 121 285 40 272 Q CD −8 109 283 54 272 Q OE1 −13 98 287 52 272 Q NE2 4 109 278 44 273 I N −20 152 251 47 273 I CA −16 161 241 49 273 I C −21 175 243 52 273 I O −13 185 243 53 273 I CB −20 156 227 52 273 I CG1 −13 143 223 52 273 I CG2 −17 167 216 51 273 I CD1 −19 137 212 38 274 S N −34 177 246 47 274 S CA −40 190 248 46 274 S C −33 197 260 50 274 S O −31 209 259 52 274 S CB −55 188 251 51 274 S OG −60 180 241 64 275 L N −31 190 271 44 275 L CA −24 196 283 42 275 L C −10 201 280 46 275 L O −7 211 285 46 275 L CB −24 186 294 41 275 L CG −37 182 300 45 275 L CD1 −36 173 312 43 275 L CD2 −45 195 303 46 276 L N −3 193 273 43 276 L CA 11 197 269 42 276 L C 10 209 260 49 276 L O 17 219 261 48 276 L CB 20 186 263 40 276 L CG 25 177 274 40 276 L CD1 28 162 270 37 276 L CD2 37 183 282 34 277 K N 1 208 250 47 277 K CA 0 219 240 45 277 K C −3 232 248 46 277 K O 2 243 244 40 277 K CB −10 217 230 47 277 K CG −7 206 219 45 277 K CD −20 204 212 55 277 K CE −24 217 204 45 277 K NZ −16 220 192 55 278 G N −12 232 258 45 278 G CA −16 243 265 45 278 G C −5 249 275 53 278 G O −5 261 278 55 279 A N 3 240 280 45 279 A CA 12 243 291 43 279 A C 27 243 288 45 279 A O 35 248 295 44 279 A CB 9 236 303 45 280 A N 31 236 277 41 280 A CA 45 235 273 42 280 A C 53 248 275 42 280 A O 62 248 282 40 280 A CB 46 231 258 44 281 F N 49 259 268 43 281 F CA 56 272 270 42 281 F C 57 276 285 45 281 F O 68 279 290 44 281 F CB 48 283 262 43 281 F CG 52 297 264 45 281 F CD1 64 301 259 49 281 F CD2 45 306 272 48 281 F CE1 69 314 260 49 281 F CE2 50 318 275 50 281 F CZ 62 323 269 48 282 E N 46 275 291 39 282 E CA 44 279 305 37 282 E C 55 272 314 39 282 E O 61 279 322 38 282 E CB 30 276 310 37 282 E CG 20 287 306 46 282 E CD 7 285 311 51 282 E OE1 6 279 322 44 282 E OE2 −3 287 304 46 283 L N 56 259 313 40 283 L CA 65 252 323 40 283 L C 79 255 318 40 283 L O 89 254 326 32 283 L CB 63 237 322 40 283 L CG 49 230 323 46 283 L CD1 49 216 329 45 283 L CD2 39 239 330 43 284 C N 81 259 305 43 284 C CA 94 261 300 47 284 C C 99 274 307 45 284 C O 110 275 312 45 284 C CB 94 261 285 52 284 C SG 110 267 278 58 285 Q N 89 284 308 38 285 Q CA 93 297 315 34 285 Q C 95 295 330 33 285 Q O 104 301 336 29 285 Q CB 81 307 313 35 285 Q CG 81 313 299 29 285 Q CD 94 317 293 50 285 Q OE1 98 312 283 46 285 Q NE2 101 326 300 43 286 L N 87 285 336 29 286 L CA 89 283 351 31 286 L C 103 276 353 34 286 L O 110 280 362 37 286 L CB 78 275 357 31 286 L CG 63 280 357 35 286 L CD1 54 268 361 35 286 L CD2 62 291 366 41 287 R N 107 268 343 27 287 R CA 120 262 344 28 287 R C 131 272 341 38 287 R O 141 273 349 40 287 R CB 120 250 334 29 287 R CG 119 236 340 25 287 R CD 121 224 330 13 287 R NE 117 212 337 25 287 R CZ 118 199 333 28 287 R NH1 121 196 320 33 287 R NH2 114 190 341 29 288 F N 130 280 331 36 288 F CA 139 291 329 36 288 F C 140 300 341 38 288 F O 150 307 343 36 288 F CB 135 299 317 39 288 F CG 141 294 304 41 288 F CD1 132 291 293 45 288 F CD2 154 291 302 44 288 F CE1 137 286 281 47 288 F CE2 159 286 290 47 288 F CZ 151 284 280 45 289 N N 129 302 349 35 289 N CA 130 311 360 35 289 N C 141 307 370 37 289 N O 149 315 375 37 289 N CB 117 314 368 37 289 N CG 117 326 377 55 289 N OD1 114 325 389 44 289 N ND2 123 337 372 33 290 T N 142 294 372 32 290 T CA 152 289 381 30 290 T C 167 291 377 37 290 T O 176 288 385 34 290 T CB 149 274 383 33 290 T OG1 153 266 372 40 290 T CG2 134 271 386 29 291 V N 169 296 365 38 291 V CA 183 298 360 37 291 V C 185 312 358 44 291 V O 195 317 353 45 291 V CB 186 290 348 39 291 V CG1 185 275 350 38 291 V CG2 177 294 336 36 292 F N 175 320 362 41 292 F CA 175 334 360 43 292 F C 183 341 372 48 292 F O 180 337 384 50 292 F CB 161 340 360 46 292 F CG 160 354 357 47 292 F CD1 163 359 344 49 292 F CD2 156 363 366 48 292 F CE1 162 372 341 50 292 F CE2 155 377 363 51 292 F CZ 158 381 350 47 293 N N 191 350 369 41 293 N CA 199 358 378 40 293 N C 194 372 377 49 293 N O 198 379 368 49 293 N CB 214 358 374 35 293 N CG 222 366 384 55 293 N OD1 218 376 390 37 293 N ND2 234 361 386 48 294 A N 187 376 387 49 294 A CA 182 390 387 49 294 A C 192 401 390 55 294 A O 190 412 386 57 294 A CB 170 392 397 50 295 E N 204 398 396 53 295 E CA 214 408 398 53 295 E C 219 412 384 58 295 E O 222 424 382 59 295 E CB 226 404 406 54 295 E CG 223 391 415 69 295 E CD 214 394 426 7 295 E OE1 206 385 430 96 295 E OE2 215 405 432 10 296 T N 220 402 375 53 296 T CA 226 404 362 51 296 T C 216 403 350 53 296 T O 221 404 339 57 296 T CB 238 396 360 61 296 T OG1 234 382 359 66 296 T CG2 247 397 372 61 297 G N 203 402 352 47 297 G CA 194 400 341 46 297 G C 199 389 331 49 297 G O 198 391 319 49 298 T N 204 378 336 43 298 T CA 209 368 328 42 298 T C 204 354 331 48 298 T O 205 349 342 48 298 T CB 225 367 330 46 298 T OG1 230 380 327 57 298 T CG2 231 357 320 44 299 W N 199 348 321 44 299 W CA 194 334 322 42 299 W C 207 326 320 39 299 W O 212 325 308 36 299 W CB 185 330 311 40 299 W CG 171 336 314 42 299 W CD1 161 330 322 45 299 W CD2 166 348 309 43 299 W NE1 151 338 322 46 299 W CE2 153 349 315 48 299 W CE3 171 358 300 44 299 W CZ2 145 360 312 47 299 W CZ3 163 369 297 46 299 W CH2 150 370 303 47 300 E N 212 320 330 32 300 E CA 224 312 330 34 300 E C 222 297 327 41 300 E O 220 289 336 44 300 E CB 231 314 343 37 300 E CG 236 328 346 38 300 E CD 240 330 360 66 300 E OE1 246 320 366 59 300 E OE2 239 341 365 76 301 C N 223 293 315 39 301 C CA 221 279 311 39 301 C C 234 271 308 49 301 C O 237 270 296 50 301 C CB 211 278 299 37 301 C SG 198 290 299 40 302 G N 240 266 318 47 302 G CA 252 258 316 46 302 G C 263 267 310 52 302 G O 266 278 316 50 303 R N 268 264 299 51 303 R CA 279 271 292 53 303 R CB 287 262 282 57 303 R CG 296 252 289 73 303 R CD 306 259 299 88 303 R C 273 283 283 54 303 R O 280 291 278 53 304 L N 260 284 282 48 304 L CA 253 295 275 48 304 L C 248 304 286 53 304 L O 245 301 297 56 304 L CB 241 290 267 48 304 L CG 243 284 254 54 304 L CD1 235 271 252 54 304 L CD2 239 294 244 59 305 S N 245 317 281 47 305 S CA 239 327 290 46 305 S C 231 335 280 56 305 S O 235 335 268 57 305 S CB 249 336 296 45 305 S OG 259 328 302 55 306 Y N 220 341 284 54 306 Y CA 212 350 276 53 306 Y C 210 363 284 60 306 Y O 204 362 295 60 306 Y CB 199 344 273 53 306 Y CG 200 331 265 55 306 Y CD1 198 319 272 58 306 Y CD2 202 331 252 53 306 Y CE1 199 307 265 62 306 Y CE2 202 319 245 53 306 Y CZ 201 307 251 61 306 Y OH 203 296 244 54 307 C N 217 373 280 60 307 C CA 217 386 287 61 307 C C 208 396 281 65 307 C O 206 397 269 65 307 C CB 231 391 289 62 307 C SG 233 404 302 67 308 L N 201 404 289 63 308 L CA 193 415 284 65 308 L C 202 427 283 76 308 L O 213 427 289 75 308 L CB 182 419 295 64 308 L CG 170 410 299 66 308 L CD1 162 404 287 66 308 L CD2 174 401 309 67 309 E N 198 437 275 78 309 E CA 206 449 273 80 309 E C 199 461 279 88 309 E O 188 465 275 89 309 E CB 208 451 258 82 309 E CG 212 439 250 93 309 E CD 227 434 253 18 309 E OE1 228 425 262 12 309 E OE2 236 439 248 15 310 D N 206 468 289 87 310 D CA 201 481 294 88 310 D C 200 491 283 92 310 D O 209 492 275 91 310 D CB 210 486 305 90 310 D CG 223 492 299 8 310 D OD1 229 486 290 9 310 D OD2 227 503 303 15 311 T N 188 498 282 90 311 T CA 186 508 272 90 311 T C 185 522 276 92 311 T O 195 529 276 93 311 T CB 173 504 263 1 311 T OG1 163 499 272 1 311 T CG2 176 492 253 98 312 A N 173 527 280 87 312 A CA 172 541 285 87 312 A C 173 540 301 92 312 A O 181 547 307 92 312 A CB 160 547 280 88 313 G N 164 532 307 87 313 G CA 163 530 321 87 313 G C 173 519 326 90 313 G O 185 521 328 89 314 G N 167 507 327 86 314 G CA 175 495 331 85 314 G C 166 486 339 86 314 G O 167 473 338 85 315 F N 158 491 348 82 315 F CA 148 484 355 81 315 F C 134 488 351 86 315 F O 126 479 345 87 315 F CB 150 486 370 82 315 F CG 152 473 378 82 315 F CD1 141 466 383 84 315 F CD2 164 466 378 84 315 F CE1 142 454 389 85 315 F CE2 166 454 385 86 315 F CZ 154 448 390 84 316 Q N 130 501 352 81 316 Q CA 117 505 348 81 316 Q C 115 505 333 83 316 Q O 103 506 328 81 316 Q CB 115 520 354 82 316 Q CG 103 527 347 94 316 Q CD 99 540 355 3 316 Q OE1 107 546 362 89 316 Q NE2 86 543 354 95 317 Q N 126 503 325 78 317 Q CA 125 501 311 78 317 Q C 122 487 307 85 317 Q O 112 484 299 85 317 Q CB 138 505 304 79 317 Q CG 137 509 289 89 317 Q CD 126 518 286 9 317 Q OE1 129 529 281 3 317 Q NE2 114 515 289 5 318 L N 129 477 313 81 318 L CA 127 463 310 80 318 L C 114 458 317 81 318 L O 107 450 311 81 318 L CB 139 455 316 80 318 L CG 153 459 311 85 318 L CD1 164 450 317 85 318 L CD2 154 458 295 86 319 L N 110 464 328 76 319 L CA 98 460 335 75 319 L C 85 462 326 80 319 L O 75 457 330 81 319 L CB 97 467 348 76 319 L CG 106 461 359 81 319 L CD1 113 472 368 80 319 L CD2 99 451 368 83 320 L N 87 469 315 77 320 L CA 75 471 307 77 320 L C 71 459 299 79 320 L O 59 457 295 81 320 L CB 78 483 297 77 320 L CG 84 495 304 83 320 L CD1 88 505 294 84 320 L CD2 74 501 314 87 321 E N 80 450 297 72 321 E CA 77 437 290 71 321 E C 72 427 299 71 321 E O 79 422 308 71 321 E CB 90 432 283 72 321 E CG 90 434 268 86 321 E CD 79 426 261 7 321 E OE1 72 432 252 91 321 E OE2 78 414 264 99 322 P N 60 423 297 64 322 P CA 53 412 306 63 322 P C 62 401 309 67 322 P O 62 396 321 67 322 P CB 41 408 297 64 322 P CG 38 419 289 68 322 P CD 50 428 288 64 323 M N 70 396 299 61 323 M CA 79 385 301 60 323 M C 90 387 311 65 323 M O 94 378 319 65 323 M CB 84 380 288 62 323 M CG 93 368 290 67 323 M SD 83 353 292 72 323 M CE 83 351 309 69 324 L N 96 399 310 60 324 L CA 107 402 319 60 324 L C 102 406 333 60 324 L O 107 400 343 59 324 L CB 115 414 313 61 324 L CG 119 411 299 69 324 L CD1 125 422 291 70 324 L CD2 128 398 298 74 325 K N 92 414 334 56 325 K CA 86 417 347 56 325 K C 82 404 354 59 325 K O 85 402 366 59 325 K CB 74 426 345 59 325 K CG 71 434 357 78 325 K CD 57 440 357 98 325 K CE 53 448 369 24 325 K NZ 41 442 376 39 326 F N 77 394 347 52 326 F CA 73 381 352 49 326 F C 85 374 359 49 326 F O 84 370 370 50 326 F CB 67 373 341 51 326 F CG 65 358 346 51 326 F CD1 53 355 352 53 326 F CD2 75 349 343 54 326 F CE1 52 342 357 55 326 F CE2 73 336 348 56 326 F CZ 62 332 355 53 327 H N 97 374 352 42 327 H CA 108 367 357 42 327 H C 114 374 370 49 327 H O 119 367 379 52 327 H CB 119 365 346 42 327 H CG 116 353 337 43 327 H ND1 121 340 341 42 327 H CD2 109 352 326 41 327 H CE1 117 332 331 40 327 H NE2 110 339 322 40 328 Y N 114 387 370 48 328 Y CA 119 394 381 48 328 Y C 110 393 393 48 328 Y O 115 392 404 49 328 Y CB 121 409 377 49 328 Y CG 134 412 370 52 328 Y CD1 134 414 356 53 328 Y CD2 146 413 377 53 328 Y CE1 146 417 349 55 328 Y CE2 158 416 370 55 328 Y CZ 157 418 356 68 328 Y OH 169 420 350 74 329 M N 97 393 390 45 329 M CA 87 391 401 47 329 M C 87 377 406 51 329 M O 85 375 418 56 329 M CB 74 396 396 50 329 M CG 73 411 396 56 329 M SD 57 414 391 64 329 M CE 48 403 402 61 330 L N 88 367 397 42 330 L CA 88 354 402 40 330 L C 101 351 410 46 330 L O 100 346 422 48 330 L CB 85 343 391 39 330 L CG 84 329 395 41 330 L CD1 73 325 405 40 330 L CD2 82 320 382 36 331 K N 112 355 405 42 331 K CA 125 353 413 42 331 K C 124 359 427 45 331 K O 129 354 436 42 331 K CB 136 359 405 45 331 K CG 150 353 409 46 331 K CD 152 339 402 37 331 K CE 164 333 409 34 331 K NZ 166 320 401 46 332 K N 118 371 427 43 332 K CA 116 379 440 43 332 K C 109 370 451 47 332 K O 112 372 463 48 332 K CB 107 391 437 44 332 K CG 110 403 445 61 332 K CD 102 415 440 87 332 K CE 99 425 451 6 332 K NZ 87 434 448 15 333 L N 100 362 448 41 333 L CA 93 353 457 38 333 L C 103 343 465 47 333 L O 100 338 476 52 333 L CB 81 346 451 36 333 L CG 70 355 444 37 333 L CD1 58 348 439 37 333 L CD2 64 364 455 37 334 Q N 114 341 459 42 334 Q CA 124 331 464 41 334 Q C 119 318 468 39 334 Q O 121 312 478 39 334 Q CB 131 337 477 43 334 Q CG 139 350 474 57 334 Q CD 145 356 487 68 334 Q OE1 154 351 492 65 334 Q NE2 138 367 492 49 335 L N 112 311 458 34 335 L CA 105 299 461 33 335 L C 115 287 462 41 335 L O 126 288 458 40 335 L CB 96 295 449 33 335 L CG 86 306 444 35 335 L CD1 77 301 433 32 335 L CD2 79 311 456 39 336 H N 110 276 467 45 336 H CA 118 264 469 46 336 H C 115 256 456 48 336 H O 106 259 449 46 336 H CB 113 257 481 49 336 H CG 117 265 494 55 336 H ND1 110 276 497 58 336 H CD2 127 264 503 58 336 H CE1 114 281 509 57 336 H NE2 125 273 512 57 337 E N 123 245 455 44 337 E CA 121 236 443 45 337 E C 108 230 443 47 337 E O 102 228 432 43 337 E CB 132 226 443 47 337 E CG 147 231 444 50 337 E CD 153 233 431 55 337 E OE1 146 235 421 38 337 E OE2 166 233 430 64 338 E N 102 227 455 45 338 E CA 89 220 456 44 338 E C 78 229 451 42 338 E O 68 224 446 37 338 E CB 87 215 470 46 338 E CG 95 204 474 53 338 E CD 108 209 480 54 338 E OE1 117 201 484 53 338 E OE2 110 221 479 44 339 E N 80 242 454 36 339 E CA 70 252 450 35 339 E C 70 254 435 38 339 E O 60 255 429 42 339 E CB 73 265 458 36 339 E CG 69 265 473 35 339 E CD 75 275 482 56 339 E OE1 85 282 478 45 339 E OE2 70 276 493 45 340 Y N 82 255 429 30 340 Y CA 83 256 415 28 340 Y C 77 244 408 37 340 Y O 70 246 397 41 340 Y CB 98 256 410 26 340 Y CG 104 270 410 29 340 Y CD1 114 274 419 30 340 Y CD2 100 280 400 31 340 Y CE1 119 286 419 28 340 Y CE2 104 293 400 29 340 Y CZ 114 296 410 32 340 Y OH 121 307 409 29 341 V N 79 232 413 32 341 V CA 74 220 406 31 341 V C 59 218 408 34 341 V O 52 213 399 33 341 V CB 81 207 411 37 341 V CG1 78 203 425 39 341 V CG2 80 197 400 37 342 L N 53 222 419 33 342 L CA 39 222 422 33 342 L C 32 233 413 37 342 L O 22 231 407 41 342 L CB 36 225 437 33 342 L CG 40 214 447 35 342 L CD1 42 219 461 34 342 L CD2 28 204 446 36 343 M N 40 244 410 33 343 M CA 35 254 400 33 343 M C 35 248 386 39 343 M O 25 250 379 41 343 M CB 45 266 400 35 343 M CG 41 279 407 36 343 M SD 54 291 406 38 343 M CE 46 301 392 33 344 Q N 45 240 383 34 344 Q CA 45 233 370 34 344 Q C 33 224 369 37 344 Q O 26 223 358 39 344 Q CB 58 225 369 35 344 Q CG 71 233 365 32 344 Q CD 83 225 363 33 344 Q OE1 94 229 367 27 344 Q NE2 80 212 361 24 345 A N 30 216 379 31 345 A CA 18 207 379 32 345 A C 5 215 377 38 345 A O −2 212 368 41 345 A CB 17 200 392 33 346 I N 3 225 386 34 346 I CA −9 233 386 34 346 I C −11 238 372 43 346 I O −22 237 367 45 346 I CB −9 244 395 35 346 I CG1 −9 238 410 36 346 I CG2 −20 253 393 30 346 I CD1 −5 248 420 39 347 S N 0 244 366 38 347 S CA −1 249 353 39 347 S C −4 237 342 46 347 S O −11 240 333 48 347 S CB 13 255 349 36 347 S OG 14 255 335 35 348 L N 3 226 344 42 348 L CA 1 214 335 40 348 L C −13 209 335 49 348 L O −19 205 325 48 348 L CB 10 203 338 38 348 L CG 10 191 330 41 348 L CD1 15 194 315 41 348 L CD2 19 180 336 31 349 F N −18 208 347 46 349 F CA −31 202 350 47 349 F C −42 212 351 53 349 F O −47 215 361 54 349 F CB −31 193 363 48 349 F CG −24 180 362 49 349 F CD1 −11 179 365 51 349 F CD2 −31 169 357 49 349 F CE1 −4 167 363 50 349 F CE2 −24 157 356 49 349 F CZ −10 156 359 46 350 S N −44 219 339 49 350 S N −44 219 340 50 350 S CA −53 230 339 49 350 S CA −53 230 339 50 350 S CB −47 242 331 51 350 S CB −47 243 333 53 350 S OG −38 250 340 56 350 S OG −51 244 319 65 350 S C −65 225 330 56 350 S C −65 226 330 57 350 S O −63 222 318 55 350 S O −63 223 318 55 351 P N −76 224 337 56 351 P CA −88 218 330 56 351 P C −93 225 318 62 351 P O −98 219 309 62 351 P CB −99 218 341 57 351 P CG −94 229 351 61 351 P CD −79 229 350 56 352 D N −91 238 318 60 352 D CA −96 247 307 60 352 D C −87 249 296 64 352 D O −85 261 291 67 352 D CB −100 260 313 63 352 D CG −89 267 320 72 352 D OD1 −78 261 323 71 352 D OD2 −90 279 324 80 353 R N −81 239 291 57 353 R CA −72 240 279 56 353 R C −79 237 266 60 353 R O −87 227 266 59 353 R CB −60 230 280 53 353 R CG −51 233 292 58 353 R CD −43 246 291 44 353 R NE −31 247 299 64 353 R CZ −25 258 302 76 353 R NH1 −30 270 297 48 353 R NH2 −14 258 309 59 354 P N −77 244 256 59 354 P CA −84 241 243 59 354 P C −82 226 240 68 354 P O −70 222 237 68 354 P CB −76 249 233 59 354 P CG −71 261 241 62 354 P CD −72 258 256 58 355 G N −92 218 240 67 355 G CA −92 204 236 67 355 G C −93 193 247 73 355 G O −90 181 245 71 356 V N −97 198 259 68 356 V CA −98 188 270 67 356 V C −111 181 272 71 356 V O −122 188 271 71 356 V CB −93 195 283 70 356 V CG1 −94 186 295 70 356 V CG2 −78 198 281 70 357 L N −111 168 273 68 357 L CA −124 161 274 67 357 L C −127 158 289 71 357 L O −136 164 294 74 357 L CB −124 148 266 66 357 L CG −120 151 252 70 357 L CD1 −117 138 244 72 357 L CD2 −130 159 244 69 358 Q N −117 152 296 62 358 Q CA −119 150 310 59 358 Q C −117 163 318 62 358 Q O −107 165 325 60 358 Q CB −108 139 315 60 358 Q CG −109 126 307 71 358 Q CD −118 116 312 86 358 Q OE1 −125 119 322 77 358 Q NE2 −119 104 306 79 359 H N −127 172 317 59 359 H N −127 172 317 58 359 H CA −127 184 324 59 359 H CA −126 184 325 58 359 H CB −140 192 319 60 359 H CB −139 193 322 59 359 H CG −138 207 319 65 359 H CG −139 206 330 63 359 H ND1 −126 213 316 67 359 H ND1 −144 218 324 65 359 H CE1 −128 226 317 66 359 H CE1 −142 228 333 64 359 H NE2 −140 229 320 67 359 H NE2 −137 223 344 64 359 H CD2 −147 217 322 67 359 H CD2 −134 209 342 64 359 H C −127 182 339 64 359 H C −126 181 339 64 359 H O −118 188 346 63 359 H O −117 186 347 63 360 R N −136 174 344 62 360 R CA −137 171 358 63 360 R C −124 165 364 68 360 R O −120 169 375 68 360 R CB −148 161 361 68 360 R CG −150 157 376 84 360 R CD −160 166 383 10 360 R NE −161 180 378 32 360 R CZ −171 188 379 52 360 R NH1 −183 183 384 44 360 R NH2 −171 200 374 36 361 V N −119 154 358 62 361 V CA −108 147 364 61 361 V C −96 156 366 61 361 V O −90 156 377 58 361 V CB −105 134 356 65 361 V CG1 −96 126 365 65 361 V CG2 −118 127 353 64 362 V N −93 164 355 56 362 V CA −81 173 355 56 362 V C −83 185 365 61 362 V O −73 190 370 60 362 V CB −79 178 341 60 362 V CG1 −68 188 340 59 362 V CG2 −77 166 331 59 363 D N −95 188 367 59 363 D CA −98 199 377 57 363 D C −95 194 391 56 363 D O −89 200 399 52 363 D CB −113 203 375 60 363 D CG −116 215 384 79 363 D OD1 −119 226 378 81 363 D OD2 −115 214 396 86 364 Q N −101 182 393 52 364 Q CA −99 176 407 53 364 Q C −84 175 409 53 364 Q O −79 178 420 54 364 Q CB −106 162 407 54 364 Q CG −121 163 406 77 364 Q CD −127 149 407 5 364 Q OE1 −121 139 411 98 364 Q NE2 −140 148 402 9 365 L N −77 171 399 49 365 L CA −62 169 399 48 365 L C −55 182 402 50 365 L O −46 183 411 50 365 L CB −57 162 387 47 365 L CG −60 147 385 46 365 L CD1 −58 142 371 46 365 L CD2 −51 139 395 35 366 Q N −59 193 396 46 366 Q CA −53 206 398 46 366 Q C −54 210 412 51 366 Q O −45 213 419 52 366 Q CB −58 216 388 47 366 Q CG −50 230 388 40 366 Q CD −58 240 379 59 366 Q OE1 −70 241 379 59 366 Q NE2 −50 248 371 46 367 E N −67 208 417 47 367 E CA −70 212 431 47 367 E C −61 205 441 50 367 E O −56 211 450 52 367 E CB −85 210 433 50 367 E CG −92 220 442 60 367 E CD −104 214 450 95 367 E OE1 −109 203 446 90 367 E OE2 −107 219 461 83 368 Q N −60 192 439 46 368 Q N −60 192 439 46 368 Q CA −51 184 448 45 368 Q CA −51 184 449 45 368 Q CB −49 170 442 46 368 Q CB −52 169 446 47 368 Q CG −60 160 445 50 368 Q CG −66 163 448 59 368 Q CD −56 146 440 51 368 Q CD −74 170 459 64 368 Q OE1 −62 140 431 29 368 Q OE1 −69 172 470 49 368 Q NE2 −47 139 448 45 368 Q NE2 −86 175 456 50 368 Q C −38 192 449 49 368 Q C −37 189 449 50 368 Q O −34 197 460 50 368 Q O −30 188 459 52 369 F N −32 194 437 44 369 F CA −19 201 436 42 369 F C −19 214 443 43 369 F O −10 216 451 41 369 F CB −14 202 422 43 369 F CG −11 189 415 42 369 F CD1 −17 186 404 44 369 F CD2 −1 181 421 45 369 F CE1 −14 174 397 45 369 F CE2 2 169 414 48 369 F CZ −4 165 402 46 370 A N −29 222 441 44 370 A CA −31 235 448 44 370 A C −31 234 463 46 370 A O −24 241 470 46 370 A CB −43 243 442 45 371 I N −39 225 468 43 371 I CA −40 222 482 42 371 I C −26 218 487 47 371 I O −22 223 498 47 371 I CB −50 211 485 46 371 I CG1 −64 216 483 45 371 I CG2 −48 205 499 47 371 I CD1 −74 206 477 53 372 T N −20 209 480 43 372 T CA −7 204 484 41 372 T C 3 216 485 45 372 T O 12 216 494 45 372 T CB −1 195 474 47 372 T OG1 −10 183 473 49 372 T CG2 13 190 477 55 373 L N 1 226 476 40 373 L CA 10 237 476 40 373 L C 6 246 488 43 373 L O 15 251 495 44 373 L CB 9 245 463 40 373 L CG 18 258 463 45 373 L CD1 32 253 463 44 373 L CD2 15 267 451 47 374 K N −6 249 489 39 374 K CA −12 257 500 39 374 K C −6 252 513 42 374 K O −2 259 521 44 374 K CB −27 255 501 40 374 K CG −34 267 505 49 374 K CD −49 267 503 54 374 K CE −55 273 516 84 374 K NZ −69 278 513 4 375 S N −7 238 515 39 375 S CA −3 233 528 40 375 S C 12 233 530 47 375 S O 17 233 541 48 375 S CB −9 219 530 49 375 S OG −21 217 523 69 376 Y N 19 231 519 44 376 Y CA 34 231 519 45 376 Y C 38 244 525 51 376 Y O 46 245 534 53 376 Y CB 40 230 505 46 376 Y CG 55 231 505 46 376 Y CD1 61 243 503 47 376 Y CD2 62 219 506 48 376 Y CE1 75 244 504 44 376 Y CE2 76 220 505 49 376 Y CZ 83 232 504 49 376 Y OH 96 233 504 43 377 I N 33 255 519 47 377 I CA 36 268 524 47 377 I C 33 270 539 53 377 I O 41 274 547 54 377 I CB 29 279 515 50 377 I CG1 35 278 501 49 377 I CG2 30 293 522 48 377 I CD1 29 287 490 39 378 E N 20 267 543 53 378 E CA 16 269 557 54 378 E C 26 262 566 63 378 E O 29 266 577 64 378 E CB 2 262 559 56 378 E CG −10 270 555 61 378 E CD −22 261 552 75 378 E OE1 −20 249 551 79 378 E OE2 −34 266 551 52 379 C N 30 250 562 60 379 C CA 40 242 570 61 379 C C 54 246 570 65 379 C O 61 244 580 65 379 C CB 39 227 565 62 379 C SG 24 218 569 66 380 N N 59 251 558 60 380 N CA 74 254 557 59 380 N C 78 268 557 61 380 N O 89 271 554 62 380 N CB 80 247 545 58 380 N CG 79 232 546 74 380 N OD1 90 225 547 73 380 N ND2 67 226 546 56 381 R N 68 277 560 60 381 R CA 71 291 561 62 381 R C 59 298 568 71 381 R O 51 306 563 70 381 R CB 73 297 547 61 381 R CG 67 289 536 66 381 R CD 72 293 521 62 381 R NE 83 303 522 68 381 R CZ 91 305 512 73 381 R NH1 90 298 501 45 381 R NH2 101 314 513 70 382 P N 56 293 581 71 382 P CA 44 298 588 71 382 P C 45 313 593 71 382 P O 36 319 598 67 382 P CB 43 289 600 73 382 P CG 56 281 601 78 382 P CD 65 285 589 73 383 Q N 57 318 592 70 383 Q CA 59 332 595 70 383 Q C 49 341 588 75 383 Q O 50 341 575 75 383 Q CB 73 337 592 72 383 Q CG 85 329 597 O 383 Q CD 85 314 592 22 383 Q OE1 81 312 580 12 383 Q NE2 88 305 600 20 384 P N 40 347 595 71 384 P CA 30 356 590 69 384 P C 35 363 577 70 384 P O 26 366 569 69 384 P CB 28 366 601 71 384 P CG 30 357 614 75 384 P CD 38 344 609 71 385 A N 48 365 576 64 385 A CA 54 372 565 64 385 A C 52 365 551 66 385 A O 57 370 541 66 385 A CB 69 375 567 65 386 H N 46 353 551 59 386 H CA 43 345 539 58 386 H C 28 341 539 56 386 H O 24 331 533 54 386 H CB 52 332 539 59 386 H CG 67 335 538 64 386 H ND1 75 332 548 66 386 H CD2 74 340 528 66 386 H CE1 88 335 545 66 386 H NE2 87 340 533 67 387 R N 20 349 545 49 387 R CA 6 347 547 47 387 R C −1 346 534 50 387 R O −11 338 532 52 387 R CB 1 359 555 43 387 R CG −14 360 556 34 387 R CD −18 369 569 27 387 R NE −32 372 567 41 387 R CZ −38 383 572 48 387 R NH1 −31 392 579 35 387 R NH2 −51 385 569 38 388 F N 2 354 524 42 388 F CA −4 354 511 38 388 F C 4 349 499 43 388 F O 2 352 488 43 388 F CB −9 368 508 37 388 F CG −21 372 516 34 388 F CD1 −22 385 521 32 388 F CD2 −32 364 518 33 388 F CE1 −33 389 528 31 388 F CE2 −42 368 526 34 388 F CZ −43 381 531 31 389 L N 15 341 503 37 389 L CA 24 335 493 38 389 L C 16 327 482 45 389 L O 20 327 470 45 389 L CB 35 327 499 37 389 L CG 45 322 489 40 389 L CD1 50 334 480 39 389 L CD2 57 315 497 34 390 F N 7 319 487 40 390 F CA −1 310 478 40 390 F C −9 318 467 47 390 F O −8 315 455 48 390 F CB −9 300 486 41 390 F CG −19 293 477 43 390 F CD1 −14 281 471 47 390 F CD2 −32 297 476 44 390 F CE1 −23 274 463 47 390 F CE2 −40 290 467 47 390 F CZ −36 278 461 46 391 L N −15 328 472 42 391 L CA −23 337 463 41 391 L C −14 344 453 44 391 L O −17 346 442 41 391 L CB −31 347 471 39 391 L CG −42 339 480 39 391 L CD1 −46 346 492 38 391 L CD2 −53 335 471 31 392 K N −2 348 458 41 392 K CA 8 355 450 41 392 K C 13 346 439 46 392 K O 14 349 427 51 392 K CB 20 359 459 42 392 K CG 17 371 467 54 392 K CD 28 373 477 58 392 K CE 28 388 482 57 392 K NZ 39 389 491 72 393 I N 16 333 442 39 393 I CA 20 323 433 36 393 I C 9 321 422 38 393 I O 12 318 411 37 393 I CB 22 310 439 37 393 I CG1 35 311 448 36 393 I CG2 22 299 429 34 393 I CD1 41 297 452 34 394 M N −4 320 427 34 394 M CA −15 317 418 33 394 M C −17 329 410 38 394 M O −21 328 399 40 394 M CB −28 315 427 34 394 M CG −30 302 434 38 394 M SD −23 287 425 44 394 M CE −35 286 412 41 395 A N −13 341 415 38 395 A CA −14 353 407 37 395 A C −4 353 395 42 395 A O −9 355 383 41 395 A CB −13 366 415 36 396 M N 8 350 397 42 396 M CA 19 348 387 44 396 M C 14 338 376 47 396 M O 16 340 364 45 396 M CB 31 343 393 47 396 M CG 36 352 404 51 396 M SD 41 368 397 57 396 M CE 59 367 400 55 397 L N 8 327 381 45 397 L CA 4 316 372 43 397 L C −7 321 363 52 397 L O −10 315 352 53 397 L CB −2 305 381 41 397 L CG 6 293 387 45 397 L CD1 −4 281 391 45 397 L CD2 17 288 378 47 398 T N −15 331 367 50 398 T CA −26 337 358 48 398 T C −19 346 348 49 398 T O −22 347 337 49 398 T CB −36 345 366 59 398 T OG1 −44 336 374 55 398 T CG2 −44 353 358 61 399 E N −9 353 353 45 399 E CA −1 363 345 44 399 E C 8 355 334 47 399 E O 11 360 324 49 399 E CB 7 372 353 45 399 E CG 18 380 346 61 399 E CD 12 392 338 90 399 E OE1 −1 393 338 91 399 E OE2 20 399 332 70 400 L N 12 343 338 45 400 L CA 20 335 329 46 400 L C 10 329 318 51 400 L O 15 327 307 50 400 L CB 26 323 337 44 400 L CG 36 314 330 44 400 L CD1 47 321 322 40 400 L CD2 42 304 339 39 401 R N −2 327 321 49 401 R CA −12 323 311 48 401 R C −16 333 301 57 401 R O −19 330 289 59 401 R CB −25 318 318 46 401 R CG −33 307 311 61 401 R CD −44 302 319 70 401 R NE −54 296 310 80 401 R CZ −60 284 312 88 401 R NH1 −57 277 323 44 401 R NH2 −69 280 303 90 402 S N −15 346 305 53 402 S CA −17 357 296 52 402 S C −6 359 287 56 402 S O −7 362 275 56 402 S CB −20 370 303 56 402 S OG −13 381 297 57 403 I N 6 358 292 55 403 I CA 19 360 285 56 403 I C 21 349 274 59 403 I O 28 351 264 59 403 I CB 31 359 294 59 403 I CG1 31 370 305 60 403 1 CG2 44 358 287 60 403 I CD1 45 376 308 57 404 N N 16 337 277 53 404 N CA 17 326 268 52 404 N C 9 330 256 56 404 N O 14 329 245 57 404 N CB 11 313 275 54 404 N CG 11 301 267 72 404 N OD1 19 299 258 77 404 N ND2 1 292 270 55 405 A N −4 334 258 53 405 A CA −13 338 248 52 405 A C −6 348 239 59 405 A O −7 347 226 59 405 A CB −25 343 254 51 406 Q N 0 358 245 58 406 Q CA 7 369 238 58 406 Q C 18 363 230 65 406 Q O 21 369 219 68 406 Q CB 12 379 248 60 406 Q CG 7 393 247 99 406 Q CD 16 403 241 40 406 Q OE1 23 410 249 37 406 Q NE2 17 403 228 38 407 H N 24 353 235 63 407 H CA 36 347 228 64 407 H C 32 339 217 61 407 H O 39 338 207 56 407 H CB 46 341 238 68 407 H CG 56 351 242 74 407 H ND1 70 347 241 77 407 H CD2 56 364 246 77 407 H CE1 77 358 245 77 407 H NE2 69 368 248 77 408 T N 21 331 218 58 408 T CA 17 323 207 58 408 T C 14 332 195 61 408 T O 16 327 184 62 408 T CB 4 316 211 64 408 T OG1 7 307 222 58 408 T CG2 −1 308 198 63 409 Q N 8 343 197 56 409 Q CA 4 352 186 53 409 Q C 16 358 179 57 409 Q O 17 358 167 60 409 Q CB −6 363 191 53 409 Q CG −19 357 195 63 409 Q CD −29 368 198 14 409 Q OE1 −28 375 209 14 409 Q NE2 −38 370 189 18 410 R N 26 362 187 52 410 R CA 38 368 182 51 410 R C 45 357 173 54 410 R O 50 360 163 53 410 R CB 48 371 194 52 410 R CG 43 381 204 72 410 R CD 55 386 212 93 410 R NE 51 390 226 9 410 R CZ 57 400 233 34 410 R NH1 67 406 227 23 410 R NH2 53 402 245 29 411 L N 46 345 179 53 411 L CA 53 334 172 53 411 L C 46 331 159 58 411 L O 52 331 148 57 411 L CB 54 322 181 52 411 L CG 60 309 175 57 411 L CD1 64 300 186 57 411 L CD2 51 303 165 56 412 L N 33 330 159 54 412 L CA 25 327 148 54 412 L C 27 338 137 58 412 L O 28 335 125 58 412 L CB 10 326 151 55 412 L CG 7 314 159 61 412 L CD1 −8 313 161 60 412 L CD2 12 301 152 64 413 R N 27 351 141 56 413 R CA 29 362 132 56 413 R C 42 362 124 62 413 R O 43 365 113 63 413 R CB 28 375 139 54 413 R CG 13 379 141 56 413 R CD 12 394 144 46 413 R NE 17 398 157 55 413 R CZ 10 398 168 71 413 R NH1 −2 394 168 67 413 R NH2 16 402 179 52 414 I N 53 358 132 60 414 I CA 66 357 126 58 414 I C 68 346 117 61 414 I O 73 347 106 61 414 I CB 77 356 137 59 414 I CG1 77 368 146 58 414 I CG2 91 354 131 59 414 I CD1 85 366 159 59 415 Q N 63 334 122 56 415 Q CA 64 322 115 55 415 Q C 57 323 101 64 415 Q O 62 317 90 63 415 Q CB 57 311 123 55 415 Q CG 54 298 116 50 415 Q CD 67 290 113 70 415 Q OE1 77 293 120 61 415 Q NE2 65 280 105 70 416 D N 47 331 100 64 416 D CA 39 333 88 64 416 D C 48 340 77 68 416 D O 49 335 66 71 416 D CB 27 342 91 66 416 D CG 18 344 79 80 416 D OD1 21 337 69 82 416 D OD2 8 352 80 87 417 I N 54 351 81 62 417 I CA 63 358 71 60 417 I C 77 352 71 63 417 I O 86 357 63 62 417 I CB 64 373 74 63 417 I CG1 74 376 85 62 417 I CG2 51 379 77 63 417 I CD1 71 390 91 55 418 H N 80 343 80 60 418 H CA 94 337 81 60 418 H C 95 324 88 64 418 H O 100 324 99 64 418 H CB 103 347 88 62 418 H CG 118 344 87 66 418 H ND1 125 339 97 69 418 H CD2 126 345 76 69 418 H CE1 138 338 93 68 418 H NE2 139 342 81 69 419 P N 90 313 82 58 419 P CA 91 300 89 55 419 P C 104 298 96 54 419 P O 114 301 92 52 419 P CB 91 290 77 56 419 P CG 87 298 65 62 419 P CD 91 312 68 58 420 F N 103 293 108 49 420 F CA 115 291 117 49 420 F C 113 280 127 54 420 F O 123 273 131 53 420 F CB 119 304 124 51 420 F CG 110 307 135 51 420 F CD1 114 305 148 53 420 F CD2 98 314 133 50 420 F CE1 106 308 159 53 420 F CE2 90 317 144 51 420 F CZ 94 314 157 50 421 A N 100 277 131 48 421 A CA 97 267 141 47 421 A C 101 253 136 48 421 A O 100 249 125 48 421 A CB 82 268 144 47 422 T N 106 245 146 42 422 T CA 109 231 143 42 422 T C 97 223 141 49 422 T O 86 228 144 51 422 T CB 117 226 155 41 422 T OG1 109 228 166 45 422 T CG2 130 232 156 34 423 P N 98 211 137 47 423 P CA 87 202 135 46 423 P C 79 201 148 48 423 P O 67 203 148 49 423 P CB 93 189 131 48 423 P CG 106 192 126 51 423 P CD 110 206 129 47 424 L N 86 198 159 43 424 L CA 80 197 173 42 424 L C 72 209 176 47 424 L O 61 208 182 47 424 L CB 90 195 184 41 424 L CG 85 192 198 45 424 L CD1 73 182 197 47 424 L CD2 95 187 208 41 425 M N 78 221 174 42 425 M CA 72 234 178 40 425 M C 59 236 169 49 425 M O 49 241 174 51 425 M CB 81 246 175 41 425 M CG 92 248 186 43 425 M SD 104 260 180 45 425 M CE 94 275 180 40 426 Q N 60 231 157 49 426 Q CA 49 232 147 48 426 Q C 37 226 153 53 426 Q O 26 231 153 56 426 Q CB 54 226 135 49 426 Q CG 58 236 124 68 426 Q CD 67 229 113 72 426 Q OE1 63 220 107 58 426 Q NE2 79 235 112 71 427 E N 39 214 159 47 427 E CA 27 207 165 47 427 E C 21 214 177 54 427 E O 9 214 179 56 427 E CB 31 193 168 47 427 E CG 35 185 156 49 427 E CD 39 171 160 64 427 E OE1 38 167 172 57 427 E OE2 43 163 151 61 428 L N 30 219 186 50 428 L CA 25 226 198 49 428 L C 17 238 194 59 428 L O 5 238 198 60 428 L CB 37 229 208 47 428 L CG 41 216 215 51 428 L CD1 56 216 221 51 428 L CD2 32 211 225 51 429 F N 23 246 186 58 429 F CA 16 258 182 59 429 F C 5 257 172 67 429 F O −3 266 169 66 429 F CB 25 270 179 61 429 F CG 34 273 190 62 429 F CD1 47 269 191 66 429 F CD2 29 281 200 65 429 F CE1 55 273 202 67 429 F CE2 37 285 211 68 429 F CZ 50 281 212 66 430 G N 3 245 166 67 430 G CA −7 242 156 66 430 G C −4 248 143 72 430 G O −13 251 135 75 431 I N 9 250 140 68 431 I CA 13 256 128 67 431 I C 11 246 116 72 431 I O 14 234 117 73 431 I CB 28 260 128 70 431 I CG1 30 271 139 70 431 I CG2 32 265 115 70 431 I CD1 44 272 145 75 444 S N −71 116 152 75 444 S CA −71 128 145 76 444 S C −62 139 152 79 444 S O −54 146 146 80 444 S CB −85 134 143 81 444 S OG −84 146 135 90 445 L N −65 141 165 73 445 L CA −56 149 173 72 445 L C −42 143 173 76 445 L O −32 151 174 76 445 L CB −61 149 188 71 445 L CG −58 162 195 74 445 L CD1 −62 174 187 74 445 L CD2 −65 162 209 75 446 T N −41 130 173 70 446 T CA −28 123 172 69 446 T C −22 124 159 71 446 T O −10 125 157 70 446 T CB −30 108 176 79 446 T OG1 −40 102 168 82 446 T CG2 −33 106 191 75 447 E N −30 123 148 66 447 E CA −25 123 134 64 447 E C −21 137 131 64 447 E O −13 138 121 64 447 E CB −36 118 124 65 447 E CG −31 119 110 85 447 E CD −35 107 101 28 447 E OE1 −43 99 106 31 447 E OE2 −30 107 90 31 448 R N −26 147 138 58 448 R CA −22 160 136 59 448 R C −10 164 145 60 448 R O −5 174 145 57 448 R CB −33 169 139 65 448 R CG −41 175 128 76 448 R CD −49 187 132 79 448 R NE −59 184 143 82 448 R CZ −61 191 154 95 448 R NH1 −54 202 156 92 448 R NH2 −71 188 162 62 449 H N −7 154 154 57 449 H CA 3 156 164 59 449 H C 12 144 165 64 449 H O 16 140 176 64 449 H CB −4 159 177 60 449 H CG −9 173 178 65 449 H ND1 −8 180 190 69 449 H CD2 −15 181 169 69 449 H CE1 −13 193 188 69 449 H NE2 −17 193 176 69 450 K N 17 139 154 59 450 K CA 25 127 153 57 450 K C 38 126 161 56 450 K O 40 115 168 55 450 K CB 28 124 138 60 450 K CG 18 114 132 77 450 K CD 19 113 117 84 450 K CE 6 115 111 99 450 K NZ O 103 105 10 451 I N 47 136 161 51 451 I CA 59 136 169 50 451 I C 56 135 184 54 451 I O 63 128 192 54 451 I CB 69 148 166 51 451 I CG1 71 150 151 51 451 I CG2 81 147 174 47 451 I CD1 79 163 146 33 452 L N 47 144 188 50 452 L CA 43 145 202 48 452 L C 38 131 207 53 452 L O 41 127 218 54 452 L CB 31 155 203 46 452 L CG 32 166 213 48 452 L CD1 18 171 217 44 452 L CD2 41 162 226 48 453 H N 29 125 199 51 453 H CA 24 112 202 53 453 H C 36 102 205 60 453 H O 38 97 216 58 453 H CB 14 106 192 54 453 H CG 6 95 196 60 453 H ND1 12 83 201 63 453 H CD2 −7 93 198 64 453 H CE1 2 75 205 63 453 H NE2 −10 81 203 64 454 R N 44 101 195 58 454 R CA 56 93 195 56 454 R C 64 95 208 61 454 R O 66 85 216 62 454 R CB 66 96 183 53 454 R CG 80 92 185 57 454 R CD 89 96 174 54 454 R NE 102 90 175 59 454 R CZ 110 87 165 76 454 R NH1 107 91 153 86 454 R NH2 122 81 167 62 455 L N 67 107 211 53 455 L CA 74 111 224 49 455 L C 67 107 236 54 455 L O 74 104 246 53 455 L CB 76 126 224 48 455 L CG 85 132 214 50 455 L CD1 89 147 218 47 455 L CD2 98 123 214 44 456 L N 54 107 236 53 456 L CA 47 103 248 54 456 L C 46 88 250 64 456 L O 45 83 261 65 456 L CB 32 108 248 53 456 L CG 32 123 249 54 456 L CD1 20 128 241 53 456 L CD2 31 127 264 50 457 Q N 47 81 238 64 457 Q CA 46 67 238 65 457 Q CB 41 62 224 66 457 Q C 59 59 242 71 457 Q O 61 48 237 70 458 E N 66 65 252 71 458 E CA 79 59 256 71 458 E C 84 64 269 77 458 E O 96 63 272 76 458 E CB 89 61 245 72 458 E CG 86 74 236 80 458 E CD 98 80 230 3 458 E OE1 102 77 219 87 458 E OE2 105 89 237 0

TABLE 3b Crystal coordinates for crystal 1 The following table contains one line for each atom in the second of the two observed PXR-LBD-L10-SRC monomers in the orthorhombic asymmetric unit. The columns are: 1) residue number, 2) 1-letter amino acid code, 3) atom name, 4) x-coordinate multiplied by 10, 5) y-coordinate multiplied by 10, 6) z-coordinate multiplied by 10, and 7) B-factor. 142 G N 611 695 −56 76 142 G CA 605 688 −68 74 142 G C 612 675 −71 73 142 G O 625 674 −70 71 143 L N 605 665 −74 66 143 L CA 611 652 −77 64 143 L C 613 652 −92 68 143 L O 607 659 −100 67 143 L CB 602 640 −73 63 143 L CG 598 639 −58 66 143 L CD1 583 634 −57 65 143 L CD2 607 629 −51 65 144 T N 622 643 −97 66 144 T CA 625 643 −111 68 144 T C 612 637 −118 74 144 T O 602 635 −111 74 144 T CB 637 634 −115 75 144 T OG1 632 620 −114 79 144 T CG2 648 636 −105 69 145 E N 614 634 −131 72 145 E CA 603 628 −138 73 145 E C 603 613 −135 74 145 E O 592 607 −132 72 145 E CB 606 629 −153 75 145 E CG 595 624 −162 91 145 E CD 583 633 −161 18 145 E OE1 583 644 −167 24 145 E OE2 573 630 −153 9 146 E N 615 607 −135 69 146 E CA 616 593 −132 68 146 E C 611 589 −119 69 146 E O 604 579 −117 69 146 E CB 631 589 −133 69 146 E CG 635 574 −130 83 146 E CD 650 572 −127 10 146 E OE1 654 577 −116 13 146 E OE2 657 566 −135 92 147 Q N 613 598 −109 64 147 Q CA 608 595 −95 62 147 Q C 593 595 −93 65 147 Q O 588 586 −88 64 147 Q CB 616 604 −85 62 147 Q CG 630 600 −84 57 147 Q CD 639 610 −77 67 147 Q OE1 635 622 −75 56 147 Q NE2 650 606 −72 67 148 R N 587 606 −98 61 148 R CA 572 607 −98 60 148 R C 565 595 −104 65 148 R O 554 592 −100 65 148 R CB 568 620 −105 59 148 R CG 571 633 −97 67 148 R CD 570 645 −106 70 148 R NE 556 648 −108 74 148 R CZ 551 653 −119 80 148 R NH1 559 656 −130 72 148 R NH2 538 656 −120 42 149 M N 571 589 −115 61 149 M CA 564 579 −121 62 149 M C 566 566 −114 57 149 M O 559 556 −115 56 149 M CB 568 578 −136 66 149 M CG 580 569 −138 74 149 M SD 580 560 −154 82 149 M CE 578 574 −166 79 150 M N 577 566 −106 52 150 M CA 581 555 −97 52 150 M C 571 553 −86 50 150 M O 566 542 −83 46 150 M CB 595 557 −93 55 150 M CG 599 547 −81 61 150 M SD 616 550 −76 66 150 M CE 624 539 −88 63 151 I N 567 565 −80 46 151 I CA 558 565 −69 45 151 I C 544 561 −74 50 151 I O 538 553 −69 50 151 I CB 558 578 −61 48 151 I CG1 572 580 −55 48 151 I CG2 548 579 −50 48 151 I CD1 574 594 −49 52 152 R N 541 567 −86 50 152 R CA 528 564 −92 50 152 R C 526 549 −94 47 152 R O 515 544 −90 43 152 R CB 527 572 −106 54 152 R CG 517 583 −106 69 152 R CD 521 595 −115 79 152 R NE 529 591 −127 77 152 R CZ 538 599 −133 82 152 R NH1 540 611 −129 66 152 R NH2 545 594 −144 64 153 E N 535 543 −101 42 153 E CA 534 529 −103 41 153 E C 532 522 −90 50 153 E O 524 513 −88 52 153 E CB 546 523 −110 43 153 E CG 544 509 −115 58 153 E CD 557 503 −121 86 153 E OE1 568 509 −121 83 153 E OE2 557 490 −125 59 154 L N 541 525 −80 46 154 L CA 541 519 −67 43 154 L C 528 519 −60 42 154 L O 522 509 −55 39 154 L CB 551 526 −58 42 154 L CG 563 518 −54 45 154 L CD1 566 508 −65 44 154 L CD2 576 526 −51 45 155 M N 522 531 −61 37 155 M CA 509 535 −55 37 155 M C 498 528 −62 45 155 M O 489 523 −55 46 155 M CB 508 550 −56 38 155 M CG 516 557 −45 41 155 M SD 510 551 −28 46 155 M CE 500 567 −23 43 156 D N 498 528 −75 42 156 D CA 488 522 −83 40 156 D C 488 507 −79 47 156 D O 477 501 −75 51 156 D CB 491 524 −98 40 156 D CG 484 514 −108 46 156 D OD1 490 505 −113 52 156 D OD2 471 516 −110 33 157 A N 499 501 −79 40 157 A CA 501 486 −75 38 157 A C 494 483 −62 41 157 A O 490 472 −60 40 157 A CB 515 482 −75 38 158 Q N 496 492 −52 36 158 Q CA 491 490 −38 35 158 Q C 476 491 −38 36 158 Q O 470 482 −33 37 158 Q CB 497 502 −29 36 158 Q CG 493 501 −14 30 158 Q CD 503 494 −5 38 158 Q OE1 507 483 −9 43 158 Q NE2 506 499 6 22 159 M N 471 501 −45 35 159 M CA 457 502 −46 36 159 M C 451 490 −52 41 159 M O 442 484 −47 39 159 M CB 454 514 −56 39 159 M CG 440 516 −59 45 159 M SD 435 509 −75 52 159 M CE 424 495 −68 50 160 K N 457 485 −63 40 160 K CA 452 473 −70 39 160 K C 453 460 −62 45 160 K O 445 451 −65 47 160 K CB 459 472 −84 39 160 K CG 456 484 −93 39 160 K CD 464 483 −106 53 160 K CE 457 493 −117 48 160 K NZ 464 492 −130 61 161 T N 463 459 −53 41 161 T CA 466 447 −47 42 161 T C 464 446 −31 48 161 T O 468 436 −25 46 161 T CB 480 441 −51 45 161 T OG1 490 450 −45 51 161 T CG2 481 441 −65 37 162 F N 460 457 −25 45 162 F CA 457 458 −11 43 162 F C 442 461 −8 47 162 F O 438 472 −11 45 162 F CB 465 470 −5 44 162 F CG 465 470 10 43 162 F CD1 472 480 17 43 162 F CD2 459 460 18 44 162 F CE1 472 480 31 45 162 F CE2 459 460 32 46 162 F CZ 466 471 38 44 163 D N 435 451 −3 47 163 D CA 421 452 −1 47 163 D C 419 457 13 51 163 D O 419 449 23 52 163 D CB 415 438 −2 49 163 D CG 401 436 4 61 163 D OD1 393 445 3 65 163 D OD2 398 424 7 57 164 T N 420 470 15 45 164 T CA 420 475 29 44 164 T C 408 471 37 50 164 T O 409 470 49 57 164 T CB 423 489 30 42 164 T OG1 413 496 21 43 164 T CG2 436 492 25 42 165 T N 396 469 31 43 165 T CA 384 465 38 42 165 T C 382 450 40 50 165 T O 372 445 46 53 165 T CB 372 470 31 50 165 T OG1 369 463 19 49 165 T CG2 373 486 28 40 166 F N 392 442 36 44 166 F CA 391 428 38 43 166 F C 378 421 34 53 166 F O 374 412 40 52 166 F CB 395 424 52 42 166 F CG 409 427 56 41 166 F CD1 418 417 59 40 166 F CD2 413 441 57 41 166 F CE1 430 420 63 40 166 F CE2 426 443 62 41 166 F CZ 435 433 64 40 167 S N 372 426 23 54 167 S CA 360 421 18 54 167 S C 361 407 12 60 167 S O 353 399 13 60 167 S CB 355 431 7 58 167 S OG 366 439 4 71 168 H N 372 405 4 59 168 H CA 374 392 −2 59 168 H C 381 382 7 57 168 H O 385 371 2 55 168 H CB 381 394 −16 62 168 H CG 374 404 −25 67 168 H ND1 361 406 −25 70 168 H CD2 379 413 −34 70 168 H CE1 357 416 −34 70 168 H NE2 369 420 −40 70 169 F N 383 385 19 52 169 F CA 388 376 29 50 169 F C 376 367 34 57 169 F O 368 371 42 57 169 F CB 394 383 41 49 169 F CG 402 374 51 47 169 F CD1 407 361 46 50 169 F CD2 402 377 64 49 169 F CE1 413 353 55 50 169 F CE2 409 368 73 51 169 F CZ 414 356 68 49 170 K N 376 354 29 54 170 K CA 364 346 32 54 170 K C 368 332 36 58 170 K O 379 327 34 58 170 K CB 354 346 21 57 170 K CG 349 360 18 66 170 K CD 343 361 3 75 170 K CE 335 374 1 83 170 K NZ 327 374 −11 88 171 N N 358 324 40 55 171 N CA 359 310 43 54 171 N C 372 308 51 57 171 N O 378 297 50 59 171 N CB 360 302 30 52 171 N CG 350 307 19 77 171 N OD1 338 310 23 79 171 N ND2 354 308 7 70 172 F N 375 317 60 48 172 F CA 386 315 69 46 172 F C 382 306 81 53 172 F O 370 304 84 54 172 F CB 392 328 75 46 172 F CG 382 337 79 45 172 F CD1 376 337 92 44 172 F CD2 377 347 70 46 172 F CE1 366 346 96 45 172 F CE2 367 356 74 49 172 F CZ 362 355 87 46 173 R N 391 301 89 50 173 R CA 389 292 101 50 173 R C 387 301 113 53 173 R O 392 312 113 50 173 R CB 400 283 103 45 173 R CG 400 271 93 43 173 R CD 412 263 96 43 173 R NE 424 270 92 59 173 R CZ 436 264 90 76 173 R NH1 437 251 93 65 173 R NH2 446 270 86 72 174 L N 380 296 123 52 174 L CA 378 304 136 50 174 L C 379 294 147 57 174 L O 377 282 146 57 174 L CB 364 310 136 48 174 L CG 361 321 126 47 174 L CD1 347 324 125 43 174 L CD2 368 333 131 47 175 P N 382 299 159 53 175 P CA 383 290 171 54 175 P C 369 283 174 64 175 P O 358 289 173 66 175 P CB 386 300 183 55 175 P CG 386 314 177 59 175 P CD 386 313 162 54 176 G N 369 270 176 61 176 G CA 357 263 179 61 176 G C 347 269 189 65 176 G O 351 277 197 61 177 V N 335 265 188 65 177 V CA 324 270 197 64 177 V C 324 262 210 66 177 V O 327 267 220 66 177 V CB 310 269 190 69 177 V CG1 308 253 188 70 177 V CG2 300 275 199 69 193 R N 619 158 297 86 193 R CA 628 169 302 86 193 R CB 639 163 310 86 193 R C 634 176 290 91 193 R O 634 188 289 92 194 E N 639 168 280 86 194 E CA 645 174 268 86 194 E CB 653 164 260 87 194 E C 634 181 259 91 194 E O 634 193 257 91 195 E N 626 172 253 86 195 E CA 615 176 244 85 195 E CB 611 165 236 87 195 E C 603 182 252 88 195 E O 592 182 247 87 196 A N 606 187 264 84 196 A CA 596 193 273 84 196 A C 599 207 277 90 196 A O 590 214 283 91 196 A CB 595 184 286 85 197 A N 611 212 275 86 197 A CA 614 226 278 85 197 A C 613 234 266 88 197 A O 618 246 265 87 197 A CB 629 227 284 85 198 K N 607 228 255 83 198 K CA 605 235 243 82 198 K C 591 242 244 81 198 K O 587 251 236 81 198 K CB 605 226 231 84 198 K CG 618 218 230 98 198 K CD 619 209 217 6 198 K CE 633 208 212 17 198 K NZ 634 204 198 26 199 W N 583 236 253 76 199 W CA 569 241 255 75 199 W C 570 254 263 83 199 W O 562 264 261 84 199 W CB 561 231 263 72 199 W CG 556 219 255 72 199 W CD1 564 209 249 75 199 W CD2 542 216 252 72 199 W NE1 555 200 243 74 199 W CE2 542 204 244 76 199 W CE3 530 222 254 74 199 W CZ2 531 198 239 75 199 W CZ3 518 217 249 76 199 W CH2 519 205 241 76 200 S N 581 256 271 81 200 S CA 583 268 279 80 200 S C 586 280 269 83 200 S O 582 292 272 85 200 S CB 593 267 289 85 200 S OG 591 276 299 96 201 Q N 592 277 258 76 201 Q CA 595 288 249 74 201 Q C 583 291 240 79 201 Q O 579 302 238 80 201 Q CB 608 286 241 75 201 Q CG 612 298 232 84 201 Q CD 610 312 238 99 201 Q OE1 616 315 248 91 201 Q NE2 603 320 231 87 202 V N 576 280 236 75 202 V CA 565 281 228 74 202 V C 553 289 234 78 202 V O 546 296 227 77 202 V CB 560 267 223 78 202 V CG1 547 268 216 77 202 V CG2 570 261 214 77 203 R N 553 289 247 76 203 R CA 542 296 255 75 203 R C 546 311 256 80 203 R O 538 319 260 80 203 R CB 541 290 269 75 203 R CG 535 276 269 79 203 R CD 533 271 283 99 203 R NE 534 256 284 10 203 R CZ 540 249 293 18 203 R NH1 547 255 303 96 203 R NH2 540 236 292 5 204 K N 559 314 254 76 204 K CA 564 327 255 76 204 K CB 580 327 257 79 204 K C 561 334 242 81 204 K O 558 346 242 81 205 D N 562 327 232 76 205 D CA 558 332 219 75 205 D C 544 338 218 79 205 D O 542 349 214 79 205 D CB 560 321 208 76 205 D CG 574 314 209 85 205 D OD1 584 321 214 84 205 D OD2 575 302 207 91 206 L N 534 330 223 72 206 L CA 520 333 223 70 206 L C 515 343 233 78 206 L O 506 351 230 79 206 L CB 513 320 224 69 206 L CG 518 309 216 72 206 L CD1 509 297 215 71 206 L CD2 520 315 202 76 207 C N 521 344 245 76 207 C CA 516 352 256 78 207 C C 515 367 253 81 207 C O 504 373 253 80 207 C CB 525 350 268 81 207 C SG 543 347 265 86 208 S N 527 373 250 80 208 S CA 528 387 247 80 208 S C 521 393 235 80 208 S O 518 405 234 80 208 S CB 543 392 247 87 208 S OG 550 384 257 100 209 L N 517 383 226 73 209 L CA 510 386 213 71 209 L C 496 381 214 75 209 L O 492 374 204 75 209 L CB 517 378 202 71 209 L CG 531 382 199 74 209 L CD1 536 371 190 75 209 L CD2 532 396 192 73 210 K N 489 383 225 71 210 K CA 475 378 227 70 210 K C 465 388 223 68 210 K O 465 400 228 67 210 K CB 473 374 241 74 210 K CG 464 363 244 86 210 K CD 470 352 253 88 210 K CE 461 347 264 78 210 K NZ 458 358 274 53 211 V N 456 385 214 61 211 V CA 445 394 209 58 211 V C 432 387 211 58 211 V O 430 374 210 55 211 V CB 447 398 195 59 211 V CG1 458 408 193 58 211 V CG2 450 386 186 59 212 S N 421 395 212 52 212 S CA 408 390 211 50 212 S C 404 394 197 54 212 S O 411 401 190 55 212 S CB 399 397 222 47 212 S OG 396 411 218 42 213 L N 393 388 192 47 213 L CA 388 390 178 46 213 L C 373 394 177 51 213 L O 365 387 184 53 213 L CB 390 376 171 47 213 L CG 388 374 156 53 213 L CD1 389 360 152 53 213 L CD2 374 380 152 56 214 Q N 370 404 169 44 214 Q CA 357 408 167 43 214 Q C 353 406 153 55 214 Q O 361 407 144 59 214 Q CB 356 423 172 43 214 Q CG 343 430 169 62 214 Q CD 340 442 178 69 214 Q OE1 345 442 189 58 214 Q NE2 332 451 173 68 215 L N 340 403 150 55 215 L CA 335 401 136 56 215 L C 321 409 135 60 215 L O 312 406 143 59 215 L CB 332 387 133 57 215 L CG 345 378 131 64 215 L CD1 344 366 139 64 215 L CD2 345 375 116 70 216 R N 320 419 126 57 216 R CA 308 426 125 57 216 R C 300 422 113 65 216 R O 306 421 102 65 216 R CB 311 441 124 55 216 R CG 319 447 136 59 216 R CD 322 462 133 75 216 R NE 336 464 128 78 216 R CZ 347 458 133 97 216 R NH1 346 449 142 83 216 R NH2 358 460 127 89 217 G N 287 419 115 63 217 G CA 279 414 104 63 217 G C 275 426 95 70 217 G O 275 437 100 68 218 E N 272 423 83 71 218 E CA 267 433 74 72 218 E C 255 439 81 77 218 E O 254 451 81 79 218 E CB 262 426 60 74 218 E CG 249 432 55 92 218 E CD 251 445 47 33 218 E OE1 260 453 51 28 218 E OE2 244 447 37 36 219 D N 247 431 87 72 219 D CA 235 435 94 71 219 D C 237 444 106 72 219 D O 227 450 111 73 219 D CB 228 422 99 73 219 D CG 236 414 109 80 219 D OD1 244 419 116 78 219 D OD2 234 401 109 83 220 G N 249 445 112 67 220 G CA 252 453 123 67 220 G C 256 446 136 70 220 G O 262 452 145 71 221 S N 254 433 137 61 221 S CA 257 424 148 57 221 S C 272 423 151 59 221 S O 280 425 143 59 221 S CB 251 411 146 58 221 S OG 256 406 133 58 222 V N 275 418 163 56 222 V CA 289 416 166 56 222 V C 292 402 173 61 222 V O 285 399 183 61 222 V CB 296 427 175 58 222 V CG1 311 426 174 57 222 V CG2 291 441 169 58 223 W N 301 395 168 56 223 W CA 306 382 174 56 223 W C 320 386 180 60 223 W O 329 389 172 62 223 W CB 307 371 164 53 223 W CG 296 362 163 54 223 W CD1 288 361 152 57 223 W CD2 291 352 172 55 223 W NE1 279 350 154 56 223 W CE2 281 345 166 57 223 W CE3 295 349 185 56 223 W CZ2 274 335 173 56 223 W CZ3 288 339 192 57 223 W CH2 278 332 186 57 224 N N 322 384 193 52 224 N CA 335 387 199 49 224 N C 340 374 205 51 224 N O 333 366 211 51 224 N CB 332 397 210 48 224 N CG 345 404 214 73 224 N OD1 351 400 224 70 224 N ND2 348 415 207 63 225 Y N 353 372 204 47 225 Y CA 360 360 209 46 225 Y C 371 364 219 53 225 Y O 382 368 214 54 225 Y CB 368 353 198 45 225 Y CG 375 341 203 43 225 Y CD1 368 330 207 45 225 Y CD2 389 340 203 44 225 Y CE1 375 318 212 45 225 Y CE2 396 329 208 45 225 Y CZ 388 318 212 55 225 Y OH 394 306 216 53 226 K N 369 362 232 50 226 K CA 380 364 241 50 226 K C 388 352 242 57 226 K O 382 341 243 57 226 K CB 375 369 255 55 226 K CG 385 368 266 75 226 K CD 383 378 277 85 226 K CE 395 387 279 4 226 K NZ 393 400 286 16 227 P N 401 352 241 58 227 P CA 409 340 241 57 227 P C 411 334 255 61 227 P O 411 342 265 59 227 P CB 423 345 235 58 227 P CG 422 361 237 62 227 P CD 409 365 240 58 228 P N 414 321 256 58 228 P CA 416 315 269 57 228 P C 429 319 275 64 228 P O 438 321 268 65 228 P CB 417 299 265 57 228 P CG 419 299 250 62 228 P CD 413 311 245 58 229 A N 429 320 289 64 229 A CA 441 324 296 65 229 A C 451 312 296 72 229 A O 447 300 294 73 229 A CB 438 328 310 66 230 D N 464 314 298 70 230 D CA 473 303 298 71 230 D C 471 293 309 76 230 D O 474 296 321 76 230 D CB 488 307 296 73 230 D CG 498 295 297 82 230 D OD1 509 297 302 81 230 D OD2 495 284 292 87 231 S N 465 281 307 73 231 S CA 462 272 317 75 231 S C 464 257 313 83 231 S O 454 250 310 85 231 S CB 448 274 323 80 231 S OG 442 261 326 90 232 G N 476 252 313 81 232 G CA 479 239 308 80 232 G C 486 241 295 85 232 G O 496 248 293 86 233 G N 479 235 284 81 233 G CA 484 237 271 81 233 G C 475 232 260 85 233 G O 466 223 263 88 234 K N 476 237 248 80 234 K CA 468 233 236 80 234 K C 457 243 232 85 234 K O 455 246 220 85 234 K CB 463 218 237 81 234 K CG 456 213 224 94 234 K CD 462 201 219 2 234 K CE 478 201 219 10 234 K NZ 484 188 224 16 235 E N 451 249 243 80 235 E CA 441 259 241 79 235 E C 447 272 236 81 235 E O 440 280 230 82 235 E CB 434 261 254 80 235 E CG 443 266 265 90 235 E CD 450 255 272 97 235 E OE1 459 257 280 69 235 E OE2 445 244 270 84 236 I N 460 273 238 73 236 I CA 468 284 235 71 236 I C 470 286 219 71 236 I O 474 296 215 71 236 I CB 481 284 241 73 236 I CG1 489 271 237 72 236 I CG2 479 282 256 75 236 I CD1 503 271 241 65 237 F N 467 275 212 66 237 F CA 468 275 198 64 237 F C 455 276 191 68 237 F O 453 271 180 68 237 F CB 474 261 193 65 237 F CG 487 257 200 65 237 F CD1 487 246 209 68 237 F CD2 499 263 198 66 237 F CE1 499 241 215 68 237 F CE2 511 259 204 68 237 F CZ 511 248 212 66 238 S N 445 281 198 63 238 S CA 431 282 193 62 238 S C 429 291 181 66 238 S O 421 290 173 68 238 S CB 421 285 204 63 238 S OG 423 298 209 64 239 L N 437 302 181 60 239 L CA 436 313 171 59 239 L C 445 310 159 61 239 L O 445 318 150 62 239 L CB 439 326 178 59 239 L CG 427 334 182 63 239 L CD1 431 347 190 63 239 L CD2 418 337 170 62 240 L N 454 300 160 58 240 L CA 464 298 150 58 240 L C 459 295 136 61 240 L O 464 301 126 60 240 L CB 474 287 154 58 240 L CG 485 291 163 62 240 L CD1 495 280 165 62 240 L CD2 491 304 159 61 241 P N 450 285 135 59 241 P CA 445 282 121 58 241 P C 440 295 115 61 241 P O 443 299 104 64 241 P CB 433 273 124 60 241 P CG 436 267 138 65 241 P CD 442 279 145 61 242 H N 432 303 123 52 242 H CA 428 316 118 51 242 H C 439 325 115 51 242 H O 440 331 104 47 242 H CB 418 322 128 53 242 H CG 415 337 127 58 242 H ND1 421 344 116 62 242 H CD2 408 346 134 63 242 H CE1 418 357 118 62 242 H NE2 410 358 129 62 243 M N 449 327 124 46 243 M CA 460 336 121 46 243 M C 467 332 108 52 243 M O 472 341 100 54 243 M CB 470 337 133 48 243 M CG 465 346 144 53 243 M SD 455 360 140 59 243 M CE 460 374 151 56 244 A N 467 319 105 45 244 A CA 473 314 93 44 244 A C 465 317 80 54 244 A O 471 320 70 58 244 A CB 475 299 95 44 245 D N 452 316 81 48 245 D CA 444 320 69 47 245 D C 446 335 66 50 245 D O 445 340 55 50 245 D CB 429 316 71 48 245 D CG 427 302 73 54 245 D OD1 436 294 70 59 245 D OD2 416 298 77 55 246 M N 446 343 77 45 246 M CA 447 358 75 43 246 M C 460 361 68 50 246 M O 461 371 61 50 246 M CB 446 365 88 45 246 M CG 450 380 87 48 246 M SD 440 388 74 51 246 M CE 427 396 85 47 247 S N 471 354 73 45 247 S CA 484 356 69 45 247 S C 486 353 55 48 247 S O 492 360 47 45 247 S CB 494 349 78 52 247 S OG 499 358 88 62 248 T N 480 341 51 45 248 T CA 480 336 37 45 248 T C 472 345 28 45 248 T O 477 349 17 46 248 T CB 475 322 36 56 248 T OG1 484 313 43 45 248 T CG2 473 318 22 52 249 Y N 461 351 33 38 249 Y CA 453 361 25 37 249 Y C 462 372 22 42 249 Y O 463 377 10 43 249 Y CB 441 366 32 35 249 Y CG 433 376 24 38 249 Y CD1 426 372 13 41 249 Y CD2 432 389 28 39 249 Y CE1 418 382 6 41 249 Y CE2 425 399 21 40 249 Y CZ 418 395 10 49 249 Y OH 411 404 2 54 250 M N 469 378 32 40 250 M CA 478 389 31 40 250 M C 489 387 22 41 250 M O 493 396 15 45 250 M CB 485 392 45 44 250 M CG 477 399 56 48 250 M SD 467 413 51 52 250 M CE 478 428 53 48 251 F N 496 375 23 35 251 F CA 508 372 15 38 251 F C 504 372 0 43 251 F O 511 377 −8 46 251 F CB 513 358 19 41 251 F CG 520 358 32 44 251 F CD1 520 346 40 47 251 F CD2 529 368 36 46 251 F CE1 527 346 52 48 251 F CE2 536 368 47 49 251 F CZ 535 356 55 48 252 K N 492 366 −3 38 252 K CA 487 366 −16 38 252 K C 485 380 −22 47 252 K O 486 382 −34 49 252 K CB 474 358 −17 38 252 K CG 477 343 −17 46 252 K CD 464 335 −14 57 252 K CE 462 323 −23 69 252 K NZ 460 311 −15 83 253 G N 482 390 −14 44 253 G CA 480 404 −19 44 253 G C 494 410 −21 46 253 G O 496 419 −29 46 254 I N 504 405 −13 42 254 I CA 518 410 −14 40 254 I C 525 403 −26 45 254 I O 532 410 −33 44 254 I CB 526 405 −1 43 254 I CG1 524 415 10 42 254 I CG2 541 405 −4 47 254 I CD1 521 429 5 40 255 I N 521 391 −29 41 255 I CA 526 384 −41 41 255 I C 520 392 −53 47 255 I O 527 395 −62 49 255 I CB 522 369 −42 42 255 I CG1 530 361 −31 43 255 I CG2 526 363 −55 36 255 I CD1 525 347 −28 40 256 S N 507 396 −52 41 256 S CA 501 404 −63 40 256 S C 508 418 −65 42 256 S O 510 423 −76 44 256 S CB 486 405 −62 41 256 S OG 481 392 −61 47 257 F N 512 423 −54 37 257 F CA 519 436 −54 36 257 F C 532 435 −62 41 257 F O 534 442 −71 40 257 F CB 521 441 −39 38 257 F CG 529 454 −38 39 257 F CD1 523 466 −42 40 257 F CD2 542 454 −33 37 257 F CE1 529 478 −41 40 257 F CE2 549 466 −33 40 257 F CZ 542 478 −36 38 258 A N 540 425 −58 41 258 A CA 553 424 −64 41 258 A C 551 422 −80 47 258 A O 558 428 −88 49 258 A CB 560 411 −59 40 259 K N 542 413 −83 42 259 K CA 539 410 −97 39 259 K C 535 421 −106 45 259 K O 536 420 −118 50 259 K CB 527 400 −97 36 259 K CG 532 386 −93 32 259 K CD 519 376 −91 23 259 K CE 509 379 −103 28 259 K NZ 499 367 −105 34 260 V N 529 432 −101 44 260 V CA 525 443 −110 45 260 V C 535 453 −112 51 260 V O 533 462 −119 50 260 V CB 511 450 −106 48 260 V CG1 501 440 −100 47 260 V CG2 514 461 −96 48 261 I N 547 452 −105 49 261 I CA 557 461 −106 49 261 I C 567 457 −117 53 261 I O 574 446 −116 53 261 I CB 566 462 −94 53 261 I CG1 558 465 −81 52 261 I CG2 576 473 −96 56 261 I CD1 567 466 −70 55 262 S N 568 464 −128 49 262 S CA 577 461 −139 49 262 S C 591 457 −135 55 262 S O 596 447 −140 55 262 S CB 578 473 −148 50 262 S OG 577 485 −140 61 263 Y N 597 463 −125 53 263 Y CA 610 460 −120 53 263 Y C 611 446 −114 54 263 Y O 622 440 −114 52 263 Y CB 615 471 −110 57 263 Y CG 616 484 −116 64 263 Y CD1 608 495 −111 67 263 Y CD2 624 487 −127 66 263 Y CE1 609 508 −117 71 263 Y CE2 625 499 −133 68 263 Y CZ 617 510 −128 83 263 Y OH 618 522 −135 91 264 F N 600 441 −108 49 264 F CA 599 428 −103 47 264 F C 598 418 −113 53 264 F O 605 407 −113 53 264 F CB 587 427 −93 46 264 F CG 588 415 −85 45 264 F CD1 596 413 −74 45 264 F CD2 580 404 −88 45 264 F CE1 597 402 −66 45 264 F CE2 580 392 −80 48 264 F CZ 588 391 −69 44 265 R N 588 420 −122 51 265 R CA 585 411 −133 52 265 R C 597 409 −142 59 265 R O 597 398 −149 61 265 R CB 573 418 −141 54 265 R CG 560 415 −135 63 265 R CD 549 418 −146 79 265 R NE 548 432 −150 73 265 R CZ 555 437 −160 92 265 R NH1 564 429 −167 95 265 R NH2 554 450 −163 63 266 D N 606 418 −143 55 266 D CA 617 416 −153 56 266 D C 629 408 −147 64 266 D O 639 406 −153 67 266 D CB 623 430 −158 57 266 D CG 612 437 −166 69 266 D OD1 603 430 −171 64 266 D OD2 613 450 −167 80 267 L N 627 403 −135 59 267 L CA 637 395 −128 56 267 L C 634 380 −131 60 267 L O 622 376 −132 58 267 L CB 635 397 −113 56 267 L CG 641 409 −105 60 267 L CD1 638 407 −90 61 267 L CD2 656 411 −107 60 268 P N 644 372 −132 58 268 P CA 642 358 −134 58 268 P C 633 352 −123 64 268 P O 635 355 −111 64 268 P CB 657 352 −132 59 268 P CG 665 363 −126 64 268 P CD 659 375 −132 59 269 I N 625 342 −127 61 269 I CA 616 336 −117 62 269 I C 622 331 −104 66 269 I O 615 331 −94 66 269 I CB 608 324 −124 65 269 I CG1 596 321 −115 66 269 I CG2 616 312 −125 68 269 I CD1 583 327 −120 73 270 E N 634 327 −104 64 270 E CA 640 322 −91 63 270 E C 643 333 −82 62 270 E O 643 332 −70 59 270 E CB 653 314 −93 65 270 E CG 651 300 −100 75 270 E CD 647 303 −115 94 270 E OE1 651 313 −120 61 270 E OE2 639 294 −120 4 271 D N 646 345 −88 56 271 D CA 648 357 −80 55 271 D C 635 362 −74 58 271 D O 633 363 −62 58 271 D CB 656 367 −88 56 271 D CG 671 365 −87 59 271 D OD1 678 373 −93 59 271 D OD2 675 355 −81 62 272 Q N 625 363 −83 49 272 Q CA 612 366 −79 47 272 Q C 607 359 −66 52 272 Q O 604 365 −56 51 272 Q CB 602 364 −90 48 272 Q CG 603 375 −101 34 272 Q CD 593 372 −113 54 272 Q OE1 595 377 −124 50 272 Q NE2 582 365 −110 58 273 I N 610 346 −66 51 273 I CA 606 337 −55 51 273 I C 614 340 −43 56 273 I O 609 340 −32 54 273 I CB 609 322 −59 55 273 I CG1 597 317 −67 55 273 I CG2 612 314 −46 57 273 I CD1 601 311 −80 62 274 S N 627 342 −45 54 274 S CA 637 344 −34 54 274 S C 634 357 −27 57 274 S O 633 357 −14 59 274 S CB 651 344 −40 57 274 S OG 656 331 −39 70 275 L N 632 368 −34 50 275 L CA 628 381 −28 49 275 L C 615 379 −20 54 275 L O 614 384 −9 56 275 L CB 626 391 −39 49 275 L CG 638 396 −47 54 275 L CD1 635 406 −59 54 275 L CD2 649 401 −38 54 276 L N 606 372 −26 47 276 L CA 593 370 −20 47 276 L C 594 363 −7 50 276 L O 588 367 3 48 276 L CB 583 363 −29 46 276 L CG 574 372 −39 51 276 L CD1 565 364 −48 52 276 L CD2 566 382 −30 54 277 K N 601 352 −7 51 277 K CA 603 344 5 50 277 K C 609 353 15 54 277 K O 607 351 27 55 277 K CB 614 333 2 52 277 K CG 609 322 −7 58 277 K CD 612 308 −1 76 277 K CE 623 308 9 72 277 K NZ 621 299 20 59 278 G N 618 361 11 51 278 G CA 626 370 20 49 278 G C 618 381 26 51 278 G O 620 384 38 54 279 A N 609 388 18 42 279 A CA 602 399 24 42 279 A C 587 398 26 49 279 A O 581 408 31 52 279 A CB 605 411 15 41 280 A N 581 387 24 42 280 A CA 567 385 26 42 280 A C 562 391 40 49 280 A O 553 399 40 48 280 A CB 563 370 25 44 281 F N 567 386 50 47 281 F CA 563 389 64 45 281 F C 565 404 66 42 281 F O 555 411 70 43 281 F CB 573 381 74 47 281 F CG 570 385 88 48 281 F CD1 559 380 95 49 281 F CD2 579 393 95 49 281 F CE1 556 384 108 47 281 F CE2 576 396 108 50 281 F CZ 565 392 114 45 282 E N 577 409 63 34 282 E CA 579 423 64 33 282 E C 569 432 57 41 282 E O 563 441 63 43 282 E CB 593 426 58 33 282 E CG 604 417 64 27 282 E CD 618 421 59 37 282 E OE1 619 430 51 46 282 E OE2 627 414 63 41 283 L N 565 428 44 38 283 L CA 556 435 36 38 283 L C 542 434 43 42 283 L O 534 444 43 37 283 L CB 556 431 22 37 283 L CG 567 436 13 42 283 L CD1 567 450 7 43 283 L CD2 581 433 19 47 284 C N 539 423 49 43 284 C CA 526 420 56 46 284 C C 525 430 68 45 284 C O 514 436 70 43 284 C CB 525 406 61 51 284 C SG 508 400 63 60 285 Q N 536 431 76 38 285 Q CA 536 439 87 36 285 Q C 535 454 83 40 285 Q O 530 462 91 40 285 Q CB 549 437 95 39 285 Q CG 550 423 100 39 285 Q CD 538 420 108 46 285 Q OE1 532 429 115 37 285 Q NE2 532 408 106 38 286 L N 541 458 72 34 286 L CA 540 472 67 33 286 L C 526 475 64 40 286 L O 521 486 67 44 286 L CB 549 475 54 31 286 L CG 564 474 58 35 286 L CD1 575 475 46 33 286 L CD2 568 485 68 36 287 R N 519 466 58 35 287 R CA 505 468 54 36 287 R C 496 468 66 42 287 R O 487 476 67 42 287 R CB 501 459 43 35 287 R CG 506 462 29 39 287 R CD 503 451 18 44 287 R NE 503 457 5 35 287 R CZ 496 452 −6 42 287 R NH1 490 440 −5 31 287 R NH2 495 458 −17 42 288 F N 498 459 76 38 288 F CA 490 458 89 37 288 F C 491 470 97 38 288 F O 482 475 104 43 288 F CB 494 446 97 40 288 F CG 486 433 95 43 288 F CD1 493 421 95 50 288 F CD2 473 433 92 46 288 F CE1 486 408 91 50 288 F CE2 465 421 89 50 288 F CZ 472 409 89 48 289 N N 503 476 96 33 289 N CA 505 489 103 33 289 N C 496 500 99 39 289 N O 493 508 107 43 289 N CB 519 494 102 28 289 N CG 522 503 114 37 289 N OD1 525 515 114 29 289 N ND2 521 499 126 34 290 T N 492 501 86 33 290 T CA 484 511 81 30 290 T C 469 511 86 37 290 T O 462 521 85 36 290 T CB 484 513 66 28 290 T OG1 477 502 59 37 290 T CG2 499 512 61 22 291 V N 464 499 89 35 291 V CA 451 496 95 35 291 V C 452 494 111 41 291 V O 443 489 117 41 291 V CB 444 484 89 36 291 V CG1 445 484 74 34 291 V CG2 451 471 93 35 292 F N 464 497 117 38 292 F CA 466 496 131 39 292 F C 461 509 139 43 292 F O 466 520 136 41 292 F CB 481 494 135 41 292 F CG 484 492 150 43 292 F CD1 478 481 156 44 292 F CD2 493 500 156 44 292 F CE1 481 479 170 44 292 F CE2 496 498 169 46 292 F CZ 490 487 176 43 293 N N 452 507 149 40 293 N CA 448 518 157 39 293 N C 456 518 170 42 293 N O 454 509 178 41 293 N CB 433 516 160 37 293 N CG 427 528 167 58 293 N OD1 435 535 174 42 293 N ND2 414 531 166 54 294 A N 465 527 171 41 294 A CA 474 527 183 42 294 A C 467 533 195 52 294 A O 469 528 206 55 294 A CB 487 535 180 42 295 E N 456 541 193 50 295 E CA 448 546 205 51 295 E C 441 534 211 56 295 E O 439 534 223 58 295 E CB 439 557 201 53 295 E CG 443 565 188 71 295 E CD 454 575 191 6 295 E OE1 460 580 181 97 295 E OE2 458 577 203 9 296 T N 436 524 203 51 296 T CA 429 513 208 47 296 T C 437 500 209 47 296 T O 432 490 215 45 296 T CB 415 511 201 54 296 T OG1 417 507 188 62 296 T CG2 407 523 202 51 297 G N 449 500 203 42 297 G CA 457 488 203 41 297 G C 452 477 195 48 297 G O 455 465 197 49 298 T N 444 481 185 46 298 T CA 437 471 177 46 298 T C 439 474 162 52 298 T O 439 486 158 52 298 T CB 422 470 180 57 298 T OG1 413 474 170 44 298 T CG2 418 478 193 51 299 W N 442 463 154 48 299 W CA 443 464 139 46 299 W C 428 463 134 49 299 W O 421 454 137 50 299 W CB 451 452 134 43 299 W CG 465 452 137 44 299 W CD1 475 459 130 47 299 W CD2 471 447 149 44 299 W NE1 487 458 137 46 299 W CE2 485 450 148 48 299 W CE3 467 440 160 45 299 W CZ2 494 447 158 47 299 W CZ3 475 437 170 46 299 W CH2 489 440 169 48 300 E N 424 473 126 44 300 E CA 411 472 120 43 300 E C 410 468 106 48 300 E O 414 475 97 49 300 E CB 405 486 122 45 300 E CG 404 490 136 57 300 E CD 405 505 138 66 300 E OE1 400 512 130 55 300 E OE2 409 509 149 79 301 C N 407 455 104 43 301 C CA 406 448 92 42 301 C C 392 447 86 47 301 C O 387 436 83 46 301 C CB 413 434 93 42 301 C SG 429 436 101 45 302 G N 386 458 83 45 302 G CA 372 457 77 46 302 G C 363 452 87 53 302 G O 362 457 98 52 303 R N 355 442 84 51 303 R CA 346 436 94 51 303 R C 352 428 105 56 303 R O 346 425 115 58 303 R CB 335 428 87 53 303 R CG 322 436 83 66 303 R CD 316 433 69 69 303 R NE 306 443 66 92 303 R CZ 302 446 53 12 303 R NH1 308 441 43 96 303 R NH2 293 456 51 97 304 L N 366 426 104 52 304 L CA 373 419 114 50 304 L C 382 428 122 50 304 L O 389 437 117 48 304 L CB 383 409 107 50 304 L CG 379 394 105 57 304 L CD1 388 388 94 58 304 L CD2 382 386 118 63 305 S N 384 426 135 47 305 S CA 393 434 144 44 305 S C 400 425 154 49 305 S O 395 416 160 45 305 S CB 385 444 152 46 305 S OG 378 454 145 62 306 Y N 413 428 155 48 306 Y CA 422 422 164 47 306 Y C 427 432 175 54 306 Y O 434 441 171 52 306 Y CB 434 415 158 46 306 Y CG 430 407 145 48 306 Y CD1 430 413 132 49 306 Y CD2 426 394 147 48 306 Y CE1 425 405 121 43 306 Y CE2 422 387 136 49 306 Y CZ 421 392 123 53 306 Y OH 418 384 113 54 307 C N 422 430 187 56 307 C CA 425 438 198 57 307 C C 435 432 207 58 307 C O 434 420 211 58 307 C CB 413 442 206 59 307 C SG 416 456 217 65 308 L N 445 440 211 56 308 L CA 455 436 220 56 308 L C 449 434 234 65 308 L O 441 443 238 64 308 L CB 466 447 221 54 308 L CG 479 443 214 54 308 L CD1 478 430 206 51 308 L CD2 486 454 207 50 309 E N 452 424 241 66 309 E CA 447 421 255 68 309 E C 455 430 265 77 309 E O 467 428 266 76 309 E CB 449 406 258 70 309 E CG 438 397 252 78 309 E CD 439 384 259 11 309 E OE1 450 379 263 3 309 E OE2 428 377 260 18 310 D N 448 438 272 80 310 D CA 455 447 282 82 310 D C 458 439 295 88 310 D O 449 432 300 87 310 D CB 448 460 284 85 310 D CG 453 471 274 3 310 D OD1 465 472 272 4 310 D OD2 444 478 268 8 311 T N 470 440 300 86 311 T CA 475 432 311 86 311 T C 483 440 322 88 311 T O 485 452 321 88 311 T CB 484 421 307 89 311 T OG1 497 426 303 80 311 T CG2 478 414 294 90 312 A N 487 433 332 85 312 A CA 495 439 343 84 312 A C 509 443 338 91 312 A O 516 434 332 92 312 A CB 497 429 355 84 313 G N 513 455 340 87 313 G CA 526 460 335 87 313 G C 523 472 326 90 313 G O 531 481 325 90 314 G N 511 471 320 85 314 G CA 507 481 311 84 314 G C 516 484 299 85 314 G O 523 475 295 84 315 F N 514 496 293 82 315 F CA 522 500 281 82 315 F C 536 495 281 88 315 F O 541 489 271 89 315 F CB 522 515 279 83 315 F CG 511 521 270 85 315 F CD1 510 516 257 87 315 F CD2 502 530 274 87 315 F CE1 500 520 248 88 315 F CE2 492 535 265 90 315 F CZ 491 530 252 88 316 Q N 542 496 292 83 316 Q CA 556 491 294 82 316 Q C 559 477 290 85 316 Q O 569 474 283 85 316 Q CB 562 495 307 83 316 Q CG 567 510 308 15 316 Q CD 562 518 295 39 316 Q OE1 551 521 293 36 316 Q NE2 572 521 287 28 317 Q N 551 468 296 82 317 Q CA 552 454 293 81 317 Q C 551 451 278 84 317 Q O 559 444 271 84 317 Q CB 542 446 301 83 317 Q CG 539 432 295 11 317 Q CD 535 422 306 46 317 Q OE1 534 410 303 46 317 Q NE2 534 426 318 38 318 L N 541 458 272 79 318 L CA 537 457 257 77 318 L C 549 461 248 81 318 L O 551 455 237 81 318 L CB 525 466 254 77 318 L CG 511 461 258 80 318 L CD1 501 470 251 80 318 L CD2 509 446 253 82 319 L N 555 472 251 75 319 L CA 566 477 243 74 319 L C 578 467 244 74 319 L O 587 467 235 74 319 L CB 570 491 248 74 319 L CG 560 501 244 81 319 L CD1 559 514 253 81 319 L CD2 559 504 229 84 320 L N 578 459 254 68 320 L CA 589 449 255 67 320 L C 589 440 243 66 320 L O 599 437 238 68 320 L CB 588 441 268 67 320 L CG 593 448 281 72 320 L CD1 607 441 285 71 320 L CD2 594 463 280 73 321 E N 577 437 238 57 321 E CA 575 428 227 56 321 E C 579 435 214 56 321 E O 575 446 211 56 321 E CB 561 422 226 57 321 E CG 558 414 214 70 321 E CD 566 402 212 92 321 E OE1 566 393 220 90 321 E OE2 573 402 201 95 322 P N 589 430 207 52 322 P CA 595 437 195 53 322 P C 586 441 184 57 322 P O 587 451 178 54 322 P CB 606 427 191 54 322 P CG 610 421 203 59 322 P CD 598 420 212 54 323 M N 577 431 181 56 323 M CA 567 434 171 57 323 M C 557 445 175 57 323 M O 553 452 167 59 323 M CB 558 421 169 61 323 M CG 547 423 160 65 323 M SD 555 421 144 70 323 M CE 565 436 142 67 324 L N 553 446 188 52 324 L CA 544 456 192 51 324 L C 550 470 193 51 324 L O 544 480 190 51 324 L CB 539 453 206 52 324 L CG 527 443 206 58 324 L CD1 528 434 194 58 324 L CD2 527 435 219 62 325 K N 563 470 197 46 325 K CA 570 483 198 44 325 K C 572 488 183 48 325 K O 570 500 181 48 325 K CB 583 480 204 45 325 K CG 593 492 204 62 325 K CD 604 490 213 81 325 K CE 615 501 212 5 325 K NZ 625 502 223 19 326 F N 575 479 174 44 326 F CA 576 483 160 41 326 F C 563 490 155 47 326 F O 564 500 148 47 326 F CB 580 471 151 42 326 F CG 579 474 136 44 326 F CD1 590 481 130 46 326 F CD2 568 471 129 48 326 F CE1 590 484 117 47 326 F CE2 568 474 115 52 326 F CZ 579 481 109 49 327 H N 552 483 157 44 327 H CA 539 489 153 45 327 H C 536 503 159 48 327 H O 532 512 151 46 327 H CB 528 478 155 48 327 H CG 526 468 144 55 327 H ND1 535 468 133 58 327 H CD2 517 459 141 58 327 H CE1 532 458 125 57 327 H NE2 521 453 129 58 328 Y N 539 505 172 45 328 Y CA 537 518 178 45 328 Y C 547 528 174 49 328 Y O 544 540 174 51 328 Y CB 536 517 193 46 328 Y CG 523 512 199 47 328 Y CD1 522 498 201 50 328 Y CD2 513 520 203 46 328 Y CE1 510 493 206 51 328 Y CE2 501 515 208 46 328 Y CZ 500 501 210 54 328 Y OH 488 496 215 57 329 M N 559 524 171 48 329 M CA 569 533 167 50 329 M C 566 539 153 51 329 M O 565 551 151 52 329 M CB 583 528 168 55 329 M CG 588 526 182 61 329 M SD 605 522 181 70 329 M CE 611 538 176 66 330 L N 563 529 144 42 330 L CA 560 532 130 40 330 L C 547 541 129 41 330 L O 546 550 121 40 330 L CB 559 520 122 39 330 L CG 559 522 107 43 330 L CD1 572 530 103 43 330 L CD2 558 509 99 45 331 K N 537 538 138 37 331 K CA 525 545 138 37 331 K C 527 560 141 42 331 K O 522 569 135 42 331 K CB 515 538 147 38 331 K CG 500 540 144 34 331 K CD 496 536 130 45 331 K CE 483 543 125 41 331 K NZ 476 537 114 48 332 K N 537 562 150 40 332 K CA 540 575 155 41 332 K C 547 584 145 51 332 K O 546 596 146 55 332 K CB 550 573 167 48 332 K CG 547 581 180 70 332 K CD 559 582 189 86 332 K CE 555 591 202 4 332 K NZ 563 587 214 13 333 L N 554 578 135 47 333 L CA 560 587 125 44 333 L C 549 593 116 46 333 L O 553 602 108 43 333 L CB 570 578 116 41 333 L CG 581 571 124 43 333 L CD1 591 563 115 40 333 L CD2 589 581 133 42 334 Q N 537 589 117 44 334 Q CA 526 594 108 44 334 Q C 530 594 93 49 334 Q O 530 605 87 50 334 Q CB 521 607 113 44 334 Q CG 517 606 127 55 334 Q CD 511 619 133 74 334 Q OE1 501 624 128 62 334 Q NE2 517 624 144 81 335 L N 533 583 87 45 335 L CA 538 582 74 41 335 L C 526 584 64 45 335 L O 516 579 67 45 335 L CB 545 569 71 39 335 L CG 557 565 79 41 335 L CD1 564 552 74 41 335 L CD2 567 577 79 35 336 H N 529 589 52 43 336 H CA 520 590 41 42 336 H C 520 577 34 44 336 H O 529 569 35 45 336 H CB 525 601 30 44 336 H CG 522 615 35 51 336 H ND1 532 624 37 54 336 H CD2 511 622 38 56 336 H CE1 527 636 41 54 336 H NE2 514 635 41 56 337 E N 510 575 26 37 337 E CA 509 563 18 36 337 E C 521 560 10 37 337 E O 527 549 9 36 337 E CB 496 563 10 37 337 E CG 483 563 18 39 337 E CD 477 549 21 65 337 E OE1 484 539 17 37 337 E OE2 467 548 29 54 338 E N 526 571 3 31 338 E CA 538 571 −6 34 338 E C 550 566 2 41 338 E O 557 557 −3 47 338 E CB 541 585 −11 35 338 E CG 530 588 −22 36 338 E CD 518 595 −15 55 338 E OE1 508 598 −22 61 338 E OE2 518 596 −3 50 339 E N 552 570 14 32 339 E CA 562 565 23 32 339 E C 561 550 27 36 339 E O 571 543 26 40 339 E CB 564 574 34 34 339 E CG 568 588 30 33 339 E CD 564 599 41 57 339 E OE1 556 596 50 63 339 E OE2 570 609 40 42 340 Y N 549 545 30 30 340 Y CA 547 531 33 28 340 Y C 550 523 21 36 340 Y O 559 514 21 42 340 Y CB 533 528 37 27 340 Y CG 530 530 52 27 340 Y CD1 523 541 56 30 340 Y CD2 535 520 61 27 340 Y CE1 521 542 70 25 340 Y CE2 532 521 75 27 340 Y CZ 524 532 79 33 340 Y OH 521 534 92 38 341 V N 544 526 10 30 341 V CA 546 519 −3 28 341 V C 561 518 −8 33 341 V O 564 507 −12 35 341 V CB 537 524 −14 31 341 V CG1 543 537 −20 32 341 V CG2 537 513 −24 30 342 L N 569 529 −6 27 342 L CA 583 528 −9 25 342 L C 591 520 2 31 342 L O 602 515 −1 29 342 L CB 591 541 −10 24 342 L CG 587 551 −22 29 342 L CD1 590 566 −18 28 342 L CD2 594 547 −34 28 343 M N 586 520 14 35 343 M CA 592 511 24 33 343 M C 590 496 19 35 343 M O 598 488 21 38 343 M CB 585 512 37 36 343 M CG 590 524 46 38 343 M SD 582 524 61 41 343 M CE 593 514 72 35 344 Q N 578 494 13 24 344 Q CA 576 480 9 24 344 Q C 586 477 −2 37 344 Q O 591 466 −2 38 344 Q CB 561 479 4 26 344 Q CG 550 479 15 27 344 Q CD 536 479 10 37 344 Q OE1 527 483 17 35 344 Q NE2 534 478 −3 33 345 A N 587 487 −12 35 345 A CA 596 484 −23 35 345 A C 610 481 −18 39 345 A O 616 472 −22 37 345 A CB 598 497 −32 35 346 I N 615 489 −8 38 346 I CA 629 487 −3 37 346 I C 630 474 3 43 346 I O 640 467 1 47 346 I CB 632 499 8 38 346 I CG1 634 512 0 36 346 I CG2 646 496 15 39 346 I CD1 630 524 8 43 347 S N 621 470 12 36 347 S CA 621 456 18 35 347 S C 621 445 7 45 347 S O 627 435 8 47 347 S CB 609 454 27 41 347 S OG 609 441 33 50 348 L N 613 448 −4 39 348 L CA 611 438 −14 38 348 L C 623 436 −23 45 348 L O 628 425 −24 48 348 L CB 599 442 −24 38 348 L CG 597 433 −36 40 348 L CD1 596 418 −32 38 348 L CD2 585 437 −45 34 349 F N 629 447 −28 40 349 F CA 641 446 −35 39 349 F C 654 446 −26 51 349 F O 663 454 −27 51 349 F CB 642 457 −46 39 349 F CG 631 456 −56 39 349 F CD1 619 462 −54 40 349 F CD2 633 446 −66 40 349 F CE1 609 460 −64 42 349 F CE2 623 445 −76 43 349 F CZ 611 452 −75 42 350 S N 655 435 −18 52 350 S CA 667 434 −9 55 350 S C 677 424 −15 64 350 S O 674 413 −17 66 350 S CB 662 430 5 58 350 S OG 657 441 12 68 351 P N 688 429 −19 63 351 P CA 698 421 −26 63 351 P C 704 410 −17 72 351 P O 707 399 −22 74 351 P CB 709 431 −30 63 351 P CG 708 442 −19 67 351 P CD 694 443 −16 62 352 D N 704 412 −3 69 352 D CA 710 402 6 67 352 D C 701 391 11 71 352 D O 703 385 22 73 352 D CB 717 408 17 70 352 D CG 709 416 26 82 352 D OD1 696 416 24 82 352 D OD2 714 424 34 86 353 R N 691 387 2 64 353 R CA 682 376 6 62 353 R C 688 362 1 69 353 R O 694 361 −10 67 353 R CB 668 377 0 55 353 R CG 660 390 3 51 353 R CD 656 392 18 55 353 R NE 649 404 20 56 353 R CZ 643 408 31 67 353 R NH1 644 401 42 52 353 R NH2 636 419 31 51 354 P N 687 352 9 66 354 P CA 692 339 5 66 354 P C 687 334 −9 74 354 P O 675 334 −12 75 354 P CB 687 329 16 68 354 P CG 678 338 24 71 354 P CD 682 352 23 66 355 G N 696 329 −18 72 355 G CA 693 324 −31 72 355 G C 691 334 −42 76 355 G O 685 331 −53 78 356 V N 695 347 −40 70 356 V CA 693 357 −50 69 356 V C 706 358 −58 75 356 V O 717 360 −52 75 356 V CB 690 371 −44 71 356 V CG1 689 382 −54 70 356 V CG2 677 371 −36 71 357 L N 705 356 −71 70 357 L CA 717 356 −80 69 357 L C 720 370 −85 70 357 L O 731 374 −88 70 357 L CB 716 346 −91 68 357 L CG 712 332 −87 72 357 L CD1 708 322 −98 72 357 L CD2 721 326 −77 73 358 Q N 709 378 −87 63 358 Q CA 711 391 −93 62 358 Q C 713 402 −82 65 358 Q O 707 413 −83 63 358 Q CB 699 395 −102 63 358 Q CG 697 385 −113 74 358 Q CD 700 391 −127 1 358 Q OE1 710 387 −134 97 358 Q NE2 693 402 −131 99 359 H N 722 399 −73 62 359 H N 722 399 −73 62 359 H CA 725 409 −62 62 359 H CA 725 408 −62 62 359 H CB 736 404 −53 63 359 H CB 738 404 −54 63 359 H CG 749 400 −60 67 359 H CG 736 392 −45 66 359 H ND1 760 396 −54 68 359 H ND1 724 389 −38 68 359 H CE1 769 392 −63 68 359 H CE1 726 378 −31 68 359 H NE2 764 393 −75 68 359 H NE2 738 373 −34 68 359 H CD2 751 398 −74 68 359 H CD2 744 381 −43 68 359 H C 727 423 −67 69 359 H C 727 423 −67 69 359 H O 722 433 −60 70 359 H O 722 432 −61 70 360 R N 734 424 −78 67 360 R CA 737 438 −84 67 360 R C 725 446 −88 68 360 R O 723 457 −84 68 360 R CB 747 437 −95 73 360 R CG 756 449 −97 87 360 R CD 763 452 −84 11 360 R NE 771 441 −79 27 360 R CZ 783 441 −73 36 360 R NH1 788 430 −69 20 360 R NH2 790 452 −73 18 361 V N 718 441 −98 62 361 V CA 706 448 −103 61 361 V C 695 451 −92 66 361 V O 688 461 −93 69 361 V CB 699 441 −115 64 361 V CG1 685 445 −117 63 361 V CG2 707 442 −127 64 362 V N 694 441 −83 59 362 V CA 685 443 −72 58 362 V C 690 454 −63 62 362 V O 682 461 −57 63 362 V CB 683 429 −65 62 362 V CG1 677 431 −51 61 362 V CG2 675 419 −73 62 363 D N 703 455 −62 59 363 D CA 708 466 −53 59 363 D C 708 480 −59 64 363 D O 709 489 −52 64 363 D CB 723 463 −49 61 363 D CG 729 473 −40 66 363 D OD1 732 471 −28 65 363 D OD2 731 484 −46 75 364 Q N 707 480 −73 60 364 Q CA 706 493 −79 60 364 Q C 692 498 −78 60 364 Q O 689 510 −75 61 364 Q CB 709 492 −94 62 364 Q CG 719 481 −97 94 364 Q CD 733 486 −94 20 364 Q OE1 737 489 −82 15 364 Q NE2 742 487 −104 11 365 L N 683 488 −79 52 365 L CA 668 490 −78 49 365 L C 666 496 −63 51 365 L O 661 506 −61 49 365 L CB 661 477 −80 49 365 L CG 659 473 −94 53 365 L CD1 657 458 −96 50 365 L CD2 648 480 −101 55 366 Q N 671 488 −54 50 366 Q CA 669 492 −40 51 366 Q C 674 506 −37 54 366 Q O 668 513 −29 57 366 Q CB 675 482 −30 52 366 Q CG 670 485 −15 59 366 Q CD 679 478 −5 59 366 Q OE1 691 478 −6 43 366 Q NE2 672 472 5 55 367 E N 685 510 −43 48 367 E CA 691 523 −41 47 367 E C 683 534 −47 47 367 E O 683 545 −42 45 367 E CB 705 524 −45 49 367 E CG 711 538 −46 66 367 E CD 726 538 −48 93 367 E OE1 733 542 −38 7 367 E OE2 730 534 −59 66 368 Q N 676 532 −59 44 368 Q CA 668 542 −65 45 368 Q C 654 543 −57 49 368 Q O 647 553 −59 51 368 Q CB 666 539 −79 47 368 Q CG 678 540 −89 57 368 Q CD 687 552 −86 68 368 Q OE1 683 563 −88 64 368 Q NE2 700 549 −82 46 369 F N 651 533 −50 43 369 F CA 638 534 −42 41 369 F C 641 541 −29 46 369 F O 634 550 −25 44 369 F CB 633 519 −39 39 369 F CG 626 512 −50 38 369 F CD1 629 499 −54 41 369 F CD2 615 519 −56 38 369 F CE1 622 493 −64 43 369 F CE2 608 512 −67 40 369 F CZ 611 499 −70 39 370 A N 653 539 −24 44 370 A CA 658 547 −12 44 370 A C 660 561 −15 48 370 A O 654 570 −9 48 370 A CB 670 541 −6 43 371 I N 666 564 −27 43 371 I CA 668 577 −32 42 371 I C 655 584 −34 48 371 I O 653 595 −31 51 371 I CB 676 578 −44 46 371 I CG1 691 578 −42 45 371 I CG2 672 589 −53 49 371 I CD1 700 572 −53 47 372 T N 645 577 −40 45 372 T CA 632 584 −43 46 372 T C 625 587 −30 51 372 T O 619 598 −28 53 372 T CB 623 576 −51 55 372 T OG1 628 573 −64 57 372 T CG2 610 584 −53 54 373 L N 627 579 −20 43 373 L CA 621 580 −7 43 373 L C 627 592 0 49 373 L O 619 600 6 47 373 L CB 624 568 1 43 373 L CG 617 568 15 47 373 L CD1 603 572 13 46 373 L CD2 619 555 23 44 374 K N 640 594 −1 47 374 K CA 647 605 5 46 374 K C 642 619 −1 53 374 K O 641 628 7 54 374 K CB 662 603 4 47 374 K CG 669 612 14 38 374 K CD 684 612 10 38 374 K CE 691 624 16 42 374 K NZ 706 622 16 56 375 S N 640 619 −14 50 375 S CA 636 631 −21 50 375 S C 621 634 −18 54 375 S O 618 645 −16 52 375 S CB 637 630 −36 57 375 S OG 651 627 −40 67 376 Y N 613 624 −19 50 376 Y CA 598 626 −15 47 376 Y C 597 633 −2 47 376 Y O 591 643 −1 45 376 Y CB 590 612 −15 48 376 Y CG 576 614 −10 47 376 Y CD1 573 616 3 48 376 Y CD2 565 615 −19 48 376 Y CE1 560 618 8 45 376 Y CE2 552 617 −15 49 376 Y CZ 550 619 −2 52 376 Y OH 537 622 3 51 377 I N 604 627 8 45 377 I CA 603 633 22 45 377 I C 607 648 22 55 377 I O 603 656 31 56 377 I CB 612 626 31 45 377 I CG1 606 612 35 44 377 I CG2 614 634 44 44 377 I CD1 615 601 40 45 378 E N 616 652 13 54 378 E CA 621 665 12 54 378 E C 612 675 6 65 378 E O 611 686 10 67 378 E CB 635 665 6 54 378 E CG 646 663 16 57 378 E CD 659 657 10 86 378 E OE1 663 661 −1 71 378 E OE2 665 648 17 90 379 C N 605 670 −4 65 379 C CA 596 679 −11 67 379 C C 583 680 −4 75 379 C O 574 688 −9 77 379 C CB 594 674 −25 68 379 C SG 611 672 −33 73 380 N N 581 673 7 71 380 N CA 568 673 14 70 380 N C 568 673 29 73 380 N O 557 671 35 71 380 N CB 559 661 9 66 380 N CG 560 660 −6 86 380 N OD1 551 666 −13 83 380 N ND2 569 652 −11 73 381 R N 579 675 36 71 381 R CA 579 674 51 71 381 R C 590 684 57 77 381 R O 599 679 63 76 381 R CB 580 660 56 68 381 R CG 574 649 47 65 381 R CD 570 636 54 58 381 R NE 561 639 65 64 381 R CZ 551 631 70 72 381 R NH1 550 619 64 42 381 R NH2 543 635 80 84 382 P N 588 697 56 75 382 P CA 597 707 60 75 382 P C 596 710 75 79 382 P O 602 720 80 79 382 P CB 594 719 52 76 382 P CG 579 716 46 80 382 P CD 575 703 52 75 383 Q N 589 702 83 74 383 Q CA 586 705 97 72 383 Q C 596 700 107 74 383 Q O 603 690 105 72 383 Q CB 572 701 101 73 383 Q CG 561 710 97 88 383 Q CD 556 707 83 6 383 Q OE1 553 695 80 93 383 Q NE2 555 717 75 10 384 P N 597 707 119 72 384 P CA 605 704 130 71 384 P C 602 689 134 76 384 P O 612 681 137 75 384 P CB 600 713 141 72 384 P CG 596 725 134 76 384 P CD 592 721 120 72 385 A N 589 686 134 70 385 A CA 585 672 137 68 385 A C 591 661 129 74 385 A O 595 651 134 76 385 A CB 570 671 136 68 386 H N 593 664 116 65 386 H CA 599 653 107 62 386 H C 614 653 104 61 386 H O 618 648 93 61 386 H CB 590 652 94 63 386 H CG 576 656 96 67 386 H ND1 569 664 87 69 386 H CD2 567 653 106 68 386 H CE1 556 665 91 68 386 H NE2 555 659 103 68 387 R N 622 658 113 51 387 R CA 637 658 111 47 387 R C 642 644 113 49 387 R O 639 637 122 50 387 R CB 643 667 122 44 387 R CG 642 682 119 48 387 R CD 649 690 130 34 387 R NE 663 688 129 31 387 R CZ 672 693 138 38 387 R NH1 668 702 147 34 387 R NH2 685 690 137 31 388 F N 651 640 104 45 388 F CA 657 627 104 42 388 F C 647 616 100 45 388 F O 650 604 101 43 388 F CB 664 623 117 44 388 F CG 673 634 122 45 388 F CD1 671 641 134 45 388 F CD2 685 637 115 46 388 F CE1 679 651 139 45 388 F CE2 694 647 120 46 388 F CZ 690 655 131 45 389 L N 636 620 93 43 389 L CA 625 610 89 43 389 L C 630 599 81 45 389 L O 628 587 83 46 389 L CB 613 617 83 43 389 L CG 602 608 81 46 389 L CD1 599 599 93 47 389 L CD2 590 615 77 44 390 F N 638 603 70 39 390 F CA 644 593 62 39 390 F C 652 582 69 43 390 F O 650 570 67 44 390 F CB 652 600 50 39 390 F CG 658 590 42 42 390 F CD1 651 581 33 46 390 F CD2 672 588 42 40 390 F CE1 657 571 26 46 390 F CE2 678 578 35 42 390 F CZ 671 570 26 42 391 L N 661 587 78 39 391 L CA 669 578 86 37 391 L C 661 570 96 38 391 L O 664 558 99 36 391 L CB 681 586 93 36 391 L CG 690 593 83 40 391 L CD1 699 603 91 37 391 L CD2 699 584 75 47 392 K N 651 576 102 34 392 K CA 642 568 111 35 392 K C 636 557 103 39 392 K O 634 546 108 37 392 K CB 631 577 117 36 392 K CG 637 589 124 42 392 K CD 630 593 136 51 392 K CE 625 607 136 64 392 K NZ 629 614 148 80 393 I N 632 560 91 37 393 I CA 624 549 84 35 393 I C 634 538 80 42 393 I O 630 527 79 40 393 I CB 618 556 71 35 393 I CG1 607 565 75 33 393 I CG2 614 545 61 39 393 I CD1 599 570 63 27 394 M N 646 542 77 41 394 M CA 656 532 73 40 394 M C 659 522 84 43 394 M O 661 510 83 41 394 M CB 668 537 66 40 394 M CG 666 545 53 43 394 M SD 659 534 40 48 394 M CE 673 525 35 43 395 A N 661 529 96 42 395 A CA 664 521 108 40 395 A C 653 511 111 43 395 A O 655 500 114 42 395 A CB 665 531 120 39 396 M N 641 516 109 40 396 M CA 629 507 111 42 396 M C 630 495 102 44 396 M O 628 484 106 42 396 M CB 617 515 109 45 396 M CG 616 528 118 52 396 M SD 606 524 133 61 396 M CE 613 510 139 57 397 L N 634 497 90 38 397 L CA 635 486 80 37 397 L C 644 476 85 47 397 L O 642 464 85 52 397 L CB 638 491 66 36 397 L CG 627 498 59 39 397 L CD1 631 502 45 40 397 L CD2 616 488 58 39 398 T N 655 481 91 42 398 T CA 666 472 97 40 398 T C 660 465 109 43 398 T O 662 453 110 43 398 T CB 677 481 101 52 398 T OG1 683 488 90 50 398 T CG2 688 472 108 52 399 E N 652 472 117 42 399 E CA 646 465 128 42 399 E CB 639 475 137 44 399 E C 636 454 123 48 399 E O 636 443 127 53 400 L N 628 458 113 41 400 L CA 618 448 107 41 400 L C 625 435 102 50 400 L O 620 424 104 48 400 L CB 609 455 97 38 400 L CG 598 447 91 42 400 L CD1 587 445 102 41 400 L CD2 592 453 79 39 401 R N 636 436 96 48 401 R N 636 436 96 49 401 R CA 644 425 91 48 401 R CA 643 425 91 49 401 R CB 655 429 82 46 401 R CB 655 428 82 49 401 R CG 663 418 77 53 401 R CG 661 417 75 60 401 R CD 676 422 71 59 401 R CD 668 421 63 74 401 R NE 683 411 63 64 401 R NE 677 432 65 84 401 R CZ 684 411 50 71 401 R CZ 690 431 65 95 401 R NH1 681 422 43 44 401 R NH1 696 420 63 77 401 R NH2 689 401 44 65 401 R NH2 698 442 68 78 401 R C 649 416 103 56 401 R C 648 416 103 56 401 R O 652 405 101 58 401 R O 651 404 102 58 402 S N 650 422 115 53 402 S CA 654 415 127 52 402 S C 642 408 133 56 402 S O 643 397 137 56 402 S CB 661 423 137 54 402 S OG 658 418 149 63 403 I N 631 415 133 51 403 I CA 618 410 138 49 403 I C 613 398 130 57 403 I O 607 389 134 56 403 I CB 607 421 138 50 403 I CG1 609 431 150 49 403 I CG2 594 415 139 50 403 I CD1 604 445 147 39 404 N N 616 399 117 56 404 N CA 613 389 107 56 404 N C 620 376 111 61 404 N O 614 365 110 62 404 N CB 617 394 93 52 404 N CG 615 383 83 62 404 N OD1 609 373 85 45 404 N ND2 619 387 71 61 405 A N 633 377 115 59 405 A CA 641 366 118 58 405 A C 636 359 130 63 405 A O 637 346 131 61 405 A CB 656 371 120 59 406 Q N 632 367 140 60 406 Q CA 627 362 153 60 406 Q C 614 355 152 64 406 Q O 612 344 158 64 406 Q CB 625 375 162 62 406 Q CG 630 373 176 2 406 Q CD 618 374 186 31 406 Q OE1 612 384 188 29 406 Q NE2 616 362 192 22 407 H N 605 360 143 61 407 H CA 592 354 141 63 407 H C 593 340 133 61 407 H O 585 331 135 59 407 H CB 583 363 134 65 407 H CG 573 370 143 71 407 H ND1 561 365 146 75 407 H CD2 575 381 151 74 407 H CE1 555 372 155 74 407 H NE2 563 382 158 74 408 T N 602 339 124 56 408 T CA 603 327 116 55 408 T C 608 316 126 61 408 T O 603 304 125 63 408 T CB 614 328 105 59 408 T OG1 611 340 97 54 408 T CG2 614 315 97 54 409 Q N 616 319 136 57 409 Q N 616 320 136 58 409 Q CA 621 310 146 56 409 Q CA 621 310 146 57 409 Q CB 633 316 153 57 409 Q CB 632 317 154 59 409 Q CG 646 317 145 56 409 Q CG 646 318 147 71 409 Q CD 650 303 139 71 409 Q CD 654 331 150 93 409 Q OE1 652 294 147 72 409 Q OE1 653 336 161 87 409 Q NE2 652 303 126 63 409 Q NE2 661 336 140 84 409 Q C 610 306 155 60 409 Q C 610 306 155 60 409 Q O 610 295 160 61 409 Q O 610 295 160 62 410 R N 601 316 158 55 410 R CA 589 313 166 54 410 R C 580 303 159 60 410 R O 574 294 165 61 410 R CB 581 326 168 53 410 R CG 582 332 182 57 410 R CD 577 347 181 76 410 R NE 585 356 190 98 410 R CZ 580 365 197 21 410 R NH1 566 367 198 14 410 R NH2 587 372 205 7 411 L N 578 307 146 59 411 L CA 568 299 138 60 411 L C 572 285 138 63 411 L O 564 276 139 64 411 L CB 568 305 124 60 411 L CG 557 301 115 65 411 L CD1 549 289 120 65 411 L CD2 548 313 112 66 412 L N 585 282 135 57 412 L CA 590 269 133 56 412 L C 589 260 146 62 412 L O 584 249 145 62 412 L CB 605 269 129 56 412 L CG 606 277 116 59 412 L CD1 621 276 111 59 412 L CD2 597 272 105 57 413 R N 592 266 157 58 413 R CA 590 260 170 58 413 R C 575 255 171 63 413 R O 572 243 174 65 413 R CB 592 270 181 56 413 R CG 607 270 186 68 413 R CD 608 281 197 72 413 R NE 619 290 193 79 413 R CZ 618 303 195 93 413 R NH1 608 308 201 68 413 R NH2 628 311 190 87 414 I N 566 265 171 58 414 I CA 552 262 173 56 414 I C 548 251 163 59 414 I O 540 242 166 60 414 I CB 543 275 170 58 414 I CG1 549 287 177 57 414 I CG2 528 273 175 55 414 1 CD1 539 298 178 51 415 Q N 553 252 151 56 415 Q CA 549 243 140 58 415 Q C 553 228 143 67 415 Q O 545 219 141 66 415 Q CB 554 247 127 59 415 Q CG 550 238 115 51 415 Q CD 536 240 110 61 415 Q OE1 530 249 115 56 415 Q NE2 532 232 101 51 416 D N 565 226 148 67 416 D CA 569 213 152 69 416 D C 559 206 161 74 416 D O 553 196 158 76 416 D CB 582 214 160 71 416 D CG 589 201 163 88 416 D OD1 591 197 174 92 416 D OD2 593 194 153 94 417 I N 557 213 173 68 417 I CA 547 209 183 67 417 I C 533 209 179 72 417 I O 524 202 184 73 417 I CB 548 220 194 70 417 I CG1 560 218 203 69 417 I CG2 536 220 202 71 417 I CD1 559 226 216 75 418 H N 529 218 169 68 418 H CA 515 219 165 67 418 H C 514 225 151 72 418 H O 511 237 150 72 418 H CB 509 229 175 67 418 H CG 494 228 175 70 418 H ND1 485 238 171 71 418 H CD2 485 218 181 71 418 H CE1 473 234 172 70 418 H NE2 473 223 178 71 419 P N 515 216 141 68 419 P CA 513 221 127 67 419 P C 501 230 126 69 419 P O 491 227 133 69 419 P CB 511 208 119 69 419 P CG 515 197 129 73 419 P CD 521 203 141 68 420 F N 502 241 118 64 420 F CA 490 250 116 62 420 F C 493 258 103 64 420 F O 483 264 98 63 420 F CB 488 259 128 64 420 F CG 498 270 129 65 420 F CD1 496 282 122 67 420 F CD2 510 268 135 66 420 F CE1 506 292 122 67 420 F CE2 520 278 136 68 420 F CZ 518 290 129 66 421 A N 505 259 98 59 421 A CA 508 267 86 58 421 A C 503 261 73 60 421 A O 505 250 70 61 421 A CB 524 269 85 58 422 T N 497 270 65 53 422 T CA 492 266 52 51 422 T C 502 261 43 54 422 T O 514 264 45 54 422 T CB 484 277 46 47 422 T OG1 493 288 45 43 422 T CG2 472 281 55 42 423 P N 498 255 32 50 423 P CA 508 251 22 50 423 P C 516 263 18 55 423 P O 529 262 16 55 423 P CB 499 245 11 52 423 P CG 489 238 19 56 423 P CD 486 247 31 52 424 L N 509 274 16 51 424 L CA 517 286 11 51 424 L C 527 291 21 54 424 L O 538 294 17 54 424 L CB 507 297 8 52 424 L CG 514 310 3 54 424 L CD1 527 307 −5 52 424 L CD2 504 318 −6 52 425 M N 523 291 34 49 425 M CA 533 296 44 46 425 M C 544 286 45 51 425 M O 555 290 48 52 425 M CB 526 296 58 47 425 M CG 519 309 61 49 425 M SD 507 306 74 52 425 M CE 517 307 88 47 426 Q N 542 273 44 49 426 Q CA 552 263 45 49 426 Q C 563 266 34 54 426 Q O 575 267 37 56 426 Q CB 547 249 43 50 426 Q CG 540 242 55 63 426 Q CD 529 232 52 83 426 Q OE1 532 221 49 86 426 Q NE2 516 236 53 63 427 E N 558 270 22 50 427 E CA 568 274 12 49 427 E C 575 287 16 52 427 E O 588 287 14 50 427 E CB 560 276 −2 51 427 E CG 551 265 −6 65 427 E CD 549 265 −21 86 427 E OE1 555 274 −28 72 427 E OE2 542 257 −27 78 428 L N 568 297 20 49 428 L CA 575 309 23 51 428 L C 585 308 34 59 428 L O 596 314 35 60 428 L CB 566 321 26 50 428 L CG 556 324 15 56 428 L CD1 544 331 20 58 428 L CD2 563 333 4 56 429 F N 582 299 44 59 429 F CA 591 297 56 62 429 F C 600 286 54 71 429 F O 610 286 61 70 429 F CB 583 296 69 64 429 F CG 574 309 71 65 429 F CD1 560 308 71 69 429 F CD2 580 321 74 67 429 F CE1 553 319 72 71 429 F CE2 572 332 76 70 429 F CZ 559 332 75 69 430 G N 598 277 45 71 430 G CA 607 266 42 73 430 G C 604 255 53 82 430 G O 610 256 64 84 431 I N 594 247 51 77 431 I CA 590 237 61 75 431 I C 588 224 53 79 431 I O 592 224 42 79 431 1 CB 577 241 69 76 431 I CG1 580 251 80 75 431 I CG2 570 229 74 76 431 I CD1 568 258 86 69 444 S N 668 253 −89 86 444 S CA 657 243 −87 85 444 S C 648 248 −76 87 444 S O 640 239 −70 87 444 S CB 664 230 −83 88 444 S OG 662 227 −69 93 445 L N 647 261 −73 80 445 L CA 638 266 −64 76 445 L C 623 265 −68 77 445 L O 614 265 −60 78 445 L CB 640 281 −61 75 445 L CG 654 287 −57 79 445 L CD1 657 300 −64 80 445 L CD2 654 289 −42 80 446 T N 620 264 −81 71 446 T CA 606 263 −85 70 446 T C 600 250 −79 70 446 T O 589 251 −75 69 446 T CB 604 262 −100 81 446 T OG1 613 253 −106 87 446 T CG2 606 276 −107 76 447 E N 608 239 −79 68 447 E CA 603 226 −74 69 447 E C 598 227 −60 77 447 E O 588 221 −56 76 447 E CB 614 216 −76 70 447 E CG 609 202 −80 79 447 E CD 619 196 −90 2 447 E OE1 630 201 −92 83 447 E OE2 615 185 −95 91 448 R N 606 234 −51 75 448 R CA 603 234 −37 75 448 R C 594 245 −33 75 448 R O 594 250 −21 74 448 R CB 617 235 −30 82 448 R CG 627 226 −36 3 448 R CD 639 224 −27 22 448 R NE 650 233 −31 38 448 R CZ 651 246 −28 46 448 R NH1 661 253 −32 27 448 R NH2 642 251 −19 30 449 H N 586 250 −42 69 449 H CA 576 260 −39 68 449 H C 567 261 −51 64 449 H O 566 271 −58 61 449 H CB 583 274 −35 70 449 H CG 591 280 −46 75 449 H ND1 586 281 −59 78 449 H CD2 603 285 −46 79 449 H CE1 595 287 −66 79 449 H NE2 605 290 −59 80 450 K N 560 250 −53 59 450 K CA 551 250 −64 59 450 K C 540 261 −64 63 450 K O 538 267 −75 65 450 K CB 545 235 −65 63 450 K CG 555 224 −63 77 450 K CD 549 211 −57 92 450 K CE 558 199 −58 13 450 K NZ 552 187 −65 28 451 1 N 535 264 −53 57 451 I CA 524 274 −52 54 451 I C 529 288 −56 55 451 I O 522 295 −64 55 451 I CB 518 275 −38 57 451 I CG1 514 262 −33 55 451 I CG2 506 285 −38 57 451 I CD1 509 262 −18 39 452 L N 540 292 −51 49 452 L CA 545 306 −55 49 452 L C 548 306 −70 56 452 L O 543 315 −77 57 452 L CB 559 308 −48 48 452 L CG 558 316 −35 50 452 L CD1 572 315 −28 48 452 L CD2 555 330 −39 49 453 H N 554 296 −75 54 453 H CA 556 295 −90 54 453 H C 543 296 −97 54 453 H O 542 304 −107 54 453 H CB 564 281 −93 58 453 H CG 568 280 −107 63 453 H ND1 580 285 −112 66 453 H CD2 562 275 −118 66 453 H CE1 581 283 −125 66 453 H NE2 570 277 −129 67 454 R N 533 288 −93 46 454 R CA 520 289 −100 44 454 R C 515 304 −100 47 454 R O 512 309 −111 49 454 R CB 510 280 −94 40 454 R CG 497 279 −102 47 454 R CD 486 271 −94 58 454 R NE 479 281 −86 70 454 R CZ 478 281 −73 77 454 R NH1 484 271 −66 72 454 R NH2 471 290 −67 66 455 L N 514 310 −88 43 455 L CA 510 324 −86 43 455 L C 518 334 −95 50 455 L O 513 344 −100 50 455 L CB 510 328 −72 41 455 L CG 501 320 −63 45 455 L CD1 504 322 −48 43 455 L CD2 487 325 −66 47 456 L N 531 332 −95 47 456 L CA 540 341 −103 47 456 L C 537 339 −118 53 456 L O 539 349 −126 51 456 L CB 554 338 −100 48 456 L CG 559 345 −87 52 456 L CD1 574 344 −87 52 456 L CD2 555 360 −87 50 457 Q N 532 328 −122 51 457 Q CA 530 325 −137 50 457 Q C 516 330 −141 56 457 Q O 514 331 −153 55 457 Q CB 531 310 −139 51 457 Q CG 545 305 −143 46 457 Q CD 545 290 −148 57 457 Q OE1 549 282 −140 51 457 Q NE2 539 288 −159 45 458 E N 507 332 −132 56 458 E CA 494 336 −136 56 458 E C 492 352 −136 61 458 E O 501 359 −133 61 458 E CB 483 329 −128 58 458 E CG 486 328 −113 73 458 E CD 476 319 −107 79 458 E OE1 475 307 −112 55 458 E OE2 469 323 −98 67

TABLE 3c Crystal coordinates for crystal 1 The following table contains one line for each atom of the solvent molecules observed in the PXR-LBD-L10-SRC monomers orthorhombic crystal form. The columns are: 1) residue number, 2) 1-letter amino acid code, 3) atom name, 4) x-coordinate multiplied by 10, 5) y-coordinate multiplied by 10, 6) z-coordinate multiplied by 10, and 7) B-factor. 1 O OW 656 599 200 58 2 O OW 729 777 100 39 3 O OW 719 677 121 41 4 O OW 413 297 143 37 5 O OW 685 721 103 45 6 O OW 530 555 104 31 7 O OW 65 325 227 51 8 O OW 483 558 59 36 9 O OW 764 845 95 56 10 O OW 19 772 28 34 11 O OW 643 629 61 38 12 O OW 174 76 152 48 13 O OW 204 190 221 41 14 O OW 771 138 108 52 15 O OW 108 139 252 58 16 O OW 587 692 251 57 17 O OW 273 302 116 71 18 O OW 184 877 155 65 19 O OW 212 46 2 44 20 O OW −2 4 43 47 21 O OW 699 693 57 57 22 O OW 650 343 3 65 23 O OW 751 368 100 57 24 O OW 771 88 240 62 25 O OW 503 334 120 69 26 O OW 799 1 131 61 27 O OW 280 783 −5 62 28 O OW 348 291 98 66 29 O OW 336 248 234 55 30 O OW 185 171 21 44 31 O OW −3 764 16 49 32 O OW 367 767 198 52 33 O OW 778 116 122 67 34 O OW 393 593 31 56 35 O OW 744 884 124 55 36 O OW 392 618 130 63 37 O OW 270 246 184 59 38 O OW 802 232 247 60 39 O OW 650 632 38 48 40 O OW 713 663 233 36 41 O OW 213 716 236 55 42 O OW 831 260 202 67 43 O OW 646 459 158 45 44 O OW 560 355 123 58 45 O OW 694 754 121 31 46 O OW 195 217 191 43 47 O OW 684 653 230 50 48 O OW 424 43 117 70 49 O OW 61 88 66 56 50 O OW 577 735 97 61 51 O OW 403 272 148 58 52 O OW 356 271 111 57 53 O OW 114 188 161 33 54 O OW 356 428 56 66 55 O OW 381 281 216 60 56 O OW 129 73 125 45 57 O OW 399 338 14 59 58 O OW 478 423 15 45 59 O OW 203 315 151 59 60 O OW 57 47 127 56 61 O OW 604 331 202 66 62 O OW 27 762 261 58 63 O OW 104 285 257 75 64 O OW 597 228 182 67 65 O OW 629 767 142 63 66 O OW 819 247 219 63 67 O OW 632 647 70 51 68 O OW 552 91 23 80 69 O OW 490 596 28 51 70 O OW 27 254 247 68 71 O OW 448 36 13 61 72 O OW 292 821 82 65 73 O OW 194 28 243 56 74 O OW 655 579 178 60 75 O OW 476 700 215 81 76 O OW 5 737 10 68 77 O OW 539 365 231 90 78 O OW 496 608 6 56 79 O OW 601 223 142 77 80 O OW 75 711 68 56 81 O OW 46 774 16 55 82 O OW 139 298 245 71 83 O OW 332 636 65 58 84 O OW 454 421 3 54 Crystal 2 Theoretical number of reflections 20767 Number of reflections in working set 19635 (94.6%) Number of reflections in test set 1051 (5.1%) Number of refined atoms (total) 2318 Number of solvent atoms 172 R-factor 0.226 R-free 0.269 RMSD bond length 0.011 Å RMSD bond angles 1.1°

TABLE 4a Crystal coordinates for crystal 2 The following table contains one line for each atom in the only observed PXR-LBD-L10-SRC monomers in the tetragonal asymmetric unit. The columns are: 1) residue number, 2) 1-letter amino acid code, 3) atom name, 4) x-coordinate multiplied by 10, 5) y-coordinate multiplied by 10, 6) z-coordinate multiplied by 10, and 7) B-factor. 142 G N −51 448 146 53 142 G CA −57 453 134 52 142 G C −63 467 136 52 142 G O −65 472 147 51 143 L N −66 474 124 47 143 L CA −72 487 125 46 143 L C −86 486 129 50 143 L O −93 476 127 49 143 L CB −71 494 111 45 143 L CG −61 506 110 48 143 L CD1 −49 503 117 47 143 L CD2 −58 509 96 49 144 T N −91 496 137 48 144 T CA −105 496 140 47 144 T C −113 501 128 53 144 T O −107 505 118 53 144 T CB −109 504 153 53 144 T OG1 −115 516 150 50 144 T CG2 −96 506 161 57 145 E N −126 502 130 48 145 E CA −135 507 119 47 145 E C −136 522 120 47 145 E O −140 529 110 45 145 E CB −149 501 121 48 145 E CG −159 503 109 61 145 E CD −152 500 96 94 145 E OE1 −145 490 95 96 145 E OE2 −155 507 86 95 146 E N −133 528 131 42 146 E CA −132 542 133 42 146 E C −119 548 128 39 146 E O −118 559 122 38 146 E CB −133 546 148 43 147 Q N −108 539 128 34 147 Q CA −95 542 123 33 147 Q C −95 542 107 34 147 Q O −92 551 101 33 147 Q CB −84 533 129 34 147 Q CG −84 535 144 37 147 Q CD −74 526 151 44 147 Q OE1 −73 514 148 32 147 Q NE2 −68 531 162 32 148 R N −101 531 102 30 148 R CA −103 530 87 30 148 R C −111 541 81 35 148 R O −110 545 70 34 148 R CB −109 516 83 28 148 R CG −101 504 88 44 148 R CD −109 491 87 58 148 R NE −110 487 73 79 148 R CZ −119 479 69 0 148 R NH1 −128 474 77 90 148 R NH2 −120 475 56 90 149 M N −121 545 89 35 149 M CA −130 556 84 37 149 M C −122 570 84 36 149 M O −124 578 75 36 149 M CB −143 557 92 41 149 M CG −152 545 91 48 149 M SD −169 547 98 56 149 M CE −167 546 116 52 150 M N −114 571 94 26 150 M CA −105 583 96 25 150 M C −95 584 84 26 150 M O −93 594 78 27 150 M CB −98 581 109 27 150 M CG −90 593 114 32 150 M SD −86 591 131 37 150 M CE −98 601 140 32 151 I N −89 573 80 21 151 I CA −80 572 69 22 151 I C −86 575 55 26 151 I O −81 582 47 23 151 I CB −72 558 68 25 151 I CG1 −63 557 81 25 151 I CG2 −64 557 56 26 151 I CD1 −56 544 83 30 152 R N −98 569 53 24 152 R CA −106 571 41 25 152 R C −111 585 39 26 152 R O −110 590 28 24 152 R CB −119 562 42 28 152 R CG −126 560 29 53 152 R CD −117 554 18 80 152 R NE −124 554 5 94 152 R CZ −121 546 −5 14 152 R NH1 −111 537 −4 4 152 R NH2 −128 547 −16 3 153 E N −115 592 49 23 153 E CA −118 606 48 24 153 E C −105 614 45 27 153 E O −106 623 37 27 153 E CB −125 611 61 25 153 E CG −123 626 64 42 153 E CD −136 634 67 65 153 E OE1 −139 636 79 55 153 E OE2 −142 638 57 60 154 L N −94 611 50 23 154 L CA −81 617 47 21 154 L C −77 615 33 21 154 L O −71 625 26 19 154 L CB −70 612 57 20 154 L CG −66 621 69 24 154 L CD1 −76 632 74 22 154 L CD2 −60 613 81 21 155 M N −78 603 28 15 155 M CA −73 600 14 13 155 M C −82 606 4 22 155 M O −78 610 −7 22 155 M CB −73 585 12 14 155 M CG −61 577 19 16 155 M SD −45 583 14 17 155 M CE −44 575 −3 16 156 D N −95 607 7 19 156 D CA −105 613 −2 19 156 D C −103 628 −3 21 156 D O −105 633 −14 18 156 D CB −119 611 5 22 156 D CG −131 614 −5 32 156 D OD1 −139 623 −2 31 156 D OD2 −131 609 −17 39 157 A N −100 635 8 17 157 A CA −96 649 7 16 157 A C −83 652 −1 17 157 A O −83 661 −9 15 157 A CB −96 656 21 17 158 Q N −73 643 1 13 158 Q CA −60 645 −7 10 158 Q C −63 644 −22 16 158 Q O −59 652 −30 15 158 Q CB −50 635 −1 11 158 Q CG −35 636 −7 10 158 Q CD −26 645 1 16 158 Q OE1 −29 657 3 17 158 Q NE2 −14 641 4 13 159 M N −70 633 −26 13 159 M CA −73 631 −40 14 159 M C −81 642 −47 19 159 M O −79 645 −59 19 159 M CB −78 617 −44 17 159 M CG −93 616 −44 20 159 M SD −102 620 −59 22 159 M CE −117 613 −53 18 160 K N −90 648 −40 14 160 K CA −98 659 −45 13 160 K C −91 672 −46 18 160 K O −95 682 −52 19 160 K CB −111 661 −36 14 160 K CG −122 651 −38 27 160 K CD −132 650 −27 29 160 K CE −144 641 −30 43 160 K NZ −155 640 −20 32 161 T N −80 674 −38 12 161 T CA −73 687 −38 11 161 T C −58 688 −41 15 161 T O −52 698 −40 14 161 T CB −75 694 −24 18 161 T OG1 −69 686 −14 17 161 T CG2 −90 694 −21 18 162 F N −51 676 −44 10 162 F CA −37 676 −48 12 162 F C −35 674 −63 19 162 F O −37 663 −68 17 162 F CB −29 666 −39 12 162 F CG −14 666 −41 12 162 F CD1 −6 656 −35 14 162 F CD2 −7 677 −48 13 162 F CE1 8 656 −37 14 162 F CE2 7 677 −49 15 162 F CZ 14 666 −44 14 163 D N −33 684 −71 19 163 D CA −31 684 −85 18 163 D C −17 679 −88 21 163 D O −8 687 −90 20 163 D CB −33 698 −91 20 163 D CG −31 698 −107 31 163 D OD1 −33 687 −113 30 163 D OD2 −29 709 −112 35 164 T N −15 666 −87 19 164 T CA −2 659 −88 20 164 T C 6 662 −101 23 164 T O 19 663 −101 20 164 T CB −3 644 −86 29 164 T OG1 −12 639 −95 31 164 T CG2 −8 641 −72 27 165 T N −1 666 −112 17 165 T CA 6 669 −124 17 165 T C 7 684 −127 21 165 T O 10 688 −138 23 165 T CB −1 662 −137 28 165 T OG1 −14 667 −139 23 165 T CG2 −1 647 −134 34 166 F N 3 693 −117 18 166 F CA 4 707 −118 17 166 F C −3 713 −131 26 166 F O 0 724 −136 26 166 F CB 18 713 −117 17 166 F CG 24 709 −103 17 166 F CD1 27 720 −94 18 166 F CD2 28 696 −100 15 166 F CE1 32 717 −81 17 166 F CE2 34 693 −88 17 166 F CZ 36 703 −78 15 167 S N −12 705 −137 24 167 S CA −19 709 −149 25 167 S C −27 722 −148 31 167 S O −29 728 −158 31 167 S CB −27 697 −155 28 167 S OG −40 698 −150 46 168 H N −30 726 −136 30 168 H CA −37 739 −134 31 168 H C −28 750 −130 29 168 H O −34 761 −127 29 168 H CB −49 737 −125 34 168 H CG −59 726 −129 40 168 H ND1 −66 727 −140 43 168 H CD2 −61 714 −123 44 168 H CE1 −74 716 −142 43 168 H NE2 −71 708 −132 44 169 F N −15 749 −129 23 169 F CA −6 760 −126 20 169 F C −2 767 −139 25 169 F O 6 762 −147 23 169 F CB 7 755 −119 20 169 F CG 17 765 −115 19 169 F CD1 12 777 −109 21 169 F CD2 30 763 −117 19 169 F CE1 22 787 −105 21 169 F CE2 40 773 −113 21 169 F CZ 35 785 −107 18 170 K N −9 778 −142 25 170 K CA −5 787 −153 27 170 K C −6 802 −151 34 170 K O −10 806 −140 34 170 K CB −14 783 −166 29 170 K CG −29 786 −164 43 171 N N −1 809 −160 32 171 N CA 0 824 −159 31 171 N C 10 829 −149 35 171 N O 9 841 −145 38 171 N CB −13 830 −155 32 171 N CG −24 829 −166 54 171 N OD1 −36 829 −163 53 171 N ND2 −20 828 −179 39 172 F N 20 821 −146 28 172 F CA 30 826 −136 25 172 F C 40 835 −142 30 172 F O 43 834 −154 27 172 F CB 37 813 −130 25 172 F CG 40 803 −140 25 172 F CD1 52 803 −147 27 172 F CD2 32 792 −142 26 172 F CE1 55 793 −156 26 172 F CE2 35 782 −151 27 172 F CZ 47 782 −158 24 173 R N 47 843 −134 27 173 R CA 58 852 −139 27 173 R C 71 844 −140 31 173 R O 72 833 −134 32 173 R CB 60 864 −130 24 173 R CG 48 873 −128 24 173 R CD 48 882 −116 24 173 R NE 43 875 −103 26 173 R CZ 45 881 −91 37 173 R NH1 50 893 −90 26 173 R NH2 41 874 −80 17 174 L N 80 848 −148 29 174 L CA 93 841 −151 29 174 L C 105 851 −150 35 174 L O 103 863 −153 35 174 L CB 93 835 −165 29 174 L CG 86 821 −166 33 174 L CD1 81 818 −180 31 174 L CD2 95 810 −161 32 175 P N 117 846 −146 34 175 P CA 128 855 −145 35 175 P C 131 863 −158 46 175 P O 132 857 −169 45 175 P CB 140 846 −141 36 175 P CG 135 832 −143 40 175 P CD 120 832 −142 35 176 G N 133 876 −157 47 176 G CA 136 885 −168 49 176 G C 144 880 −179 59 176 G O 155 874 −177 59 177 V N 140 882 −191 58 177 V CA 147 877 −203 59 177 V C 160 885 −206 64 177 V O 159 896 −213 64 177 V CB 138 878 −216 63 198 K N 241 962 53 90 198 K CA 233 962 66 89 198 K C 225 949 67 93 198 K O 229 939 72 92 198 K CB 225 975 67 92 199 W N 212 951 64 91 199 W CA 203 940 64 90 199 W C 204 931 52 94 199 W O 199 919 52 94 199 W CB 188 945 65 89 200 S N 212 936 42 90 200 S CA 215 928 30 90 200 S C 224 916 32 93 200 S O 221 905 26 93 200 S CB 221 938 20 94 201 Q N 234 918 41 90 201 Q CA 243 907 44 89 201 Q C 235 895 49 92 201 Q O 238 884 45 91 201 Q CB 253 911 55 90 202 V N 225 898 57 88 202 V CA 216 888 62 88 202 V C 208 882 51 92 202 V O 208 870 49 92 202 V CB 206 894 72 92 203 R N 203 891 42 88 203 R CA 195 887 30 88 203 R C 202 877 21 92 203 R O 196 873 11 90 203 R CB 190 899 23 88 204 K N 214 873 25 90 204 K CA 222 864 17 90 204 K C 217 849 21 94 204 K O 225 839 19 94 204 K CB 237 865 20 92 205 D N 205 849 27 91 205 D CA 199 836 31 91 205 D C 196 828 18 95 205 D O 193 816 19 95 205 D CB 186 838 38 93 205 D CG 188 848 50 99 205 D OD1 191 842 61 100 205 D OD2 185 860 49 99 206 L N 197 835 7 92 206 L CA 194 829 −6 92 206 L C 205 820 −11 97 206 L O 203 810 −18 97 206 L CB 191 840 −17 92 206 L CG 179 849 −15 97 206 L CD1 178 854 0 97 206 L CD2 180 861 −24 99 207 C N 217 823 −6 93 207 C CA 229 816 −10 93 207 C C 228 801 −9 97 207 C O 232 793 −18 97 207 C CB 241 820 −1 93 208 S N 221 796 2 93 208 S CA 219 782 5 92 208 S C 209 776 −5 95 208 S O 204 765 −3 94 208 S CB 214 780 19 96 208 S OG 203 787 22 6 209 L N 205 783 −15 89 209 L CA 196 779 −25 87 209 L C 201 780 −39 86 209 L O 207 791 −43 87 209 L CB 183 787 −24 88 209 L CG 176 787 −10 93 209 L CD1 176 801 −4 94 209 L CD2 162 781 −10 97 210 K N 200 770 −47 76 210 K CA 205 770 −61 73 210 K C 198 760 −70 68 210 K O 202 748 −71 68 210 K CB 220 768 −61 75 210 K CG 229 780 −62 92 210 K CD 222 792 −69 1 210 K CE 229 805 −67 11 210 K NZ 223 816 −74 18 211 V N 188 765 −78 58 211 V CA 181 756 −87 55 211 V C 180 762 −101 50 211 V O 180 774 −103 50 211 V CB 167 753 −82 58 211 V CG1 167 746 −69 58 211 V CG2 158 766 −82 58 212 S N 181 753 −111 40 212 S CA 178 757 −125 37 212 S C 163 753 −128 37 212 S O 158 744 −121 34 212 S CB 188 751 −134 36 212 S OG 186 737 −137 40 213 L N 158 759 −138 30 213 L CA 144 757 −142 30 213 L C 142 751 −156 33 213 L O 149 755 −165 34 213 L CB 136 771 −142 31 213 L CG 121 771 −140 38 213 L CD1 117 784 −133 39 213 L CD2 114 770 −154 43 214 Q N 133 741 −157 26 214 Q CA 130 736 −171 25 214 Q C 115 736 −174 30 214 Q O 107 731 −165 29 214 Q CB 137 723 −174 25 214 Q CG 133 717 −187 23 214 Q CD 139 704 −190 50 214 Q OE1 151 701 −189 47 214 Q NE2 130 694 −193 45 215 L N 111 741 −185 26 215 L CA 97 741 −190 26 215 L C 94 733 −202 33 215 L O 99 736 −213 31 215 L CB 92 755 −192 27 215 L CG 95 766 −181 35 215 L CD1 88 779 −184 37 215 L CD2 89 760 −168 42 216 R N 87 722 −201 33 216 R CA 85 713 −213 35 216 R C 72 717 −220 43 216 R O 61 717 −214 44 216 R CB 85 698 −210 32 216 R CG 98 692 −205 41 216 R CD 98 678 −199 50 216 R NE 92 677 −186 54 216 R CZ 97 683 −175 64 216 R NH1 108 691 −176 36 216 R NH2 91 682 −163 57 217 G N 74 721 −232 41 217 G CA 62 726 −240 42 217 G C 53 714 −244 51 217 G O 58 704 −250 48 218 E N 40 716 −242 53 218 E CA 30 706 −245 55 218 E C 31 702 −260 59 218 E O 22 695 −265 59 218 E CB 16 712 −243 57 219 D N 41 707 −266 55 219 D CA 44 705 −281 53 219 D C 57 698 −285 52 219 D O 58 696 −297 51 219 D CB 42 718 −288 55 219 D CG 53 728 −285 63 219 D OD1 65 725 −285 63 219 D OD2 49 740 −283 66 220 G N 66 697 −276 47 220 G CA 79 691 −280 45 220 G C 91 700 −277 46 220 G O 102 695 −276 46 221 S N 88 713 −276 42 221 S CA 99 723 −272 40 221 S C 102 723 −257 40 221 S O 95 718 −249 37 221 S CB 95 737 −277 43 221 S OG 83 741 −270 48 222 V N 114 729 −254 37 222 V CA 120 730 −241 36 222 V C 127 743 −238 38 222 V O 134 748 −247 36 222 V CB 130 718 −238 41 222 V CG1 137 720 −225 41 222 V CG2 123 705 −238 41 223 W N 124 750 −227 34 223 W CA 131 762 −223 34 223 W C 138 759 −210 36 223 W O 132 753 −201 35 223 W CB 120 772 −220 33 223 W CG 116 781 −231 34 223 W CD1 104 780 −237 36 223 W CD2 123 791 −237 34 223 W NE1 103 789 −247 35 223 W CE2 115 796 −248 37 223 W CE3 136 796 −236 35 223 W CZ2 120 807 −256 36 223 W CZ3 141 806 −244 35 223 W CH2 132 812 −254 36 224 N N 151 762 −209 32 224 N CA 159 760 −196 32 224 N C 164 774 −191 37 224 N O 169 782 −199 37 224 N CB 170 750 −198 36 224 N CG 175 745 −185 78 224 N OD1 184 751 −179 74 224 N ND2 171 733 −180 76 225 Y N 165 775 −178 32 225 Y CA 170 787 −172 34 225 Y C 181 783 −162 39 225 Y O 179 773 −155 37 225 Y CB 159 795 −165 35 225 Y CG 165 807 −157 38 225 Y CD1 165 820 −163 40 225 Y CD2 169 806 −144 39 225 Y CE1 170 831 −157 41 225 Y CE2 174 817 −137 39 225 Y CZ 174 830 −143 50 225 Y OH 179 841 −137 53 226 K N 192 790 −162 39 226 K CA 203 789 −152 41 226 K C 205 802 −145 49 226 K O 207 812 −152 47 226 K CB 216 785 −160 43 226 K CG 216 773 −168 58 227 P N 204 802 −132 51 227 P CA 204 814 −124 53 227 P C 218 821 −126 62 227 P O 228 816 −131 60 227 P CB 203 810 −110 54 227 P CG 209 796 −110 58 227 P CD 209 790 −124 52 228 P N 219 834 −121 63 228 P CA 231 841 −121 65 228 P C 239 839 −108 74 228 P O 236 830 −100 75 228 P CB 227 856 −121 66 228 P CG 213 856 −115 70 228 P CD 207 842 −117 65 229 A N 250 847 −106 73 229 A CA 258 846 −94 74 229 A C 258 859 −85 80 229 A O 257 870 −91 78 229 A CB 273 843 −98 75 230 D N 258 857 −72 80 230 D CA 258 869 −63 81 230 D C 269 878 −67 86 230 D O 281 873 −68 85 230 D CB 258 865 −49 83 230 D CG 254 876 −39 96 230 D OD1 257 888 −42 97 230 D OD2 247 873 −30 3 231 S N 267 890 −71 84 231 S CA 277 900 −75 85 231 S C 272 914 −75 90 231 S O 274 921 −86 90 231 S CB 283 896 −88 88 232 G N 266 919 −64 88 232 G CA 261 932 −63 88 232 G C 248 933 −56 93 232 G O 247 929 −44 93 233 G N 237 936 −63 88 233 G CA 224 937 −56 87 233 G C 213 929 −63 90 233 G O 216 917 −67 91 234 K N 201 934 −65 85 234 K CA 190 928 −71 84 234 K C 191 914 −76 85 234 K O 186 905 −70 85 234 K CB 185 937 −83 87 235 E N 199 912 −87 78 235 E CA 202 899 −93 77 235 E C 197 886 −86 76 235 E O 193 876 −92 75 235 E CB 216 898 −97 78 236 I N 199 885 −72 70 236 I CA 195 874 −65 69 236 I C 180 873 −63 67 236 I O 174 862 −60 66 236 I CB 202 873 −51 72 236 I CG1 204 888 −46 73 236 I CG2 215 866 −53 74 236 I CD1 215 889 −36 78 237 F N 173 884 −66 58 237 F CA 158 885 −65 55 237 F C 151 883 −79 50 237 F O 140 888 −80 48 237 F CB 155 900 −61 57 237 F CG 161 904 −48 59 237 F CD1 167 916 −47 62 237 F CD2 161 896 −37 62 237 F CE1 172 920 −35 63 237 F CE2 166 900 −25 65 237 F CZ 172 912 −24 63 238 S N 158 878 −89 42 238 S CA 151 876 −101 40 238 S C 141 864 −101 37 238 S O 132 864 −109 37 238 S CB 161 875 −113 43 238 S OG 171 865 −111 53 239 L N 143 855 −92 31 239 L CA 135 843 −91 30 239 L C 124 844 −80 31 239 L O 115 835 −79 30 239 L CB 143 831 −89 31 239 L CG 146 820 −100 36 239 L CD1 137 821 −112 35 239 L CD2 161 819 −103 40 240 L N 123 856 −73 26 240 L CA 113 858 −62 25 240 L C 99 859 −67 29 240 L O 90 853 −60 28 240 L CB 117 871 −54 24 240 L CG 128 870 −43 29 240 L CD1 130 884 −36 28 240 L CD2 126 859 −33 28 241 P N 96 866 −78 24 241 P CA 82 866 −83 23 241 P C 77 852 −87 25 241 P O 65 849 −83 23 241 P CB 83 876 −94 26 241 P CG 95 885 −91 30 241 P CD 105 876 −84 25 242 H N 85 844 −95 20 242 H CA 80 830 −99 19 242 H C 77 822 −86 23 242 H O 67 815 −85 21 242 H CB 91 823 −108 19 242 H CG 88 808 −110 22 242 H ND1 78 804 −119 23 242 H CD2 94 797 −105 23 242 H CE1 78 790 −119 23 242 H NE2 87 786 −110 24 243 M N 87 822 −77 23 243 M CA 86 815 −64 24 243 M C 74 819 −56 20 243 M O 67 810 −51 16 243 M CB 99 815 −56 28 243 M CG 111 809 −64 36 243 M SD 108 790 −68 44 243 M CE 125 784 −71 40 244 A N 71 832 −56 16 244 A CA 59 837 −49 15 244 A C 46 832 −56 19 244 A O 36 829 −49 20 244 A CB 59 852 −49 16 245 D N 46 830 −69 17 245 D CA 35 825 −77 17 245 D C 33 810 −74 19 245 D O 21 806 −72 17 245 D CB 35 829 −92 19 245 D CG 33 844 −95 27 245 D OD1 28 851 −86 25 245 D OD2 36 848 −106 21 246 M N 44 802 −74 15 246 M CA 43 787 −71 13 246 M C 38 785 −57 17 246 M O 30 777 −54 17 246 M CB 56 781 −73 15 246 M CG 57 766 −69 16 246 M SD 44 755 −77 19 246 M CE 54 747 −91 16 247 S N 43 793 −48 16 247 S CA 40 792 −33 17 247 S C 24 795 −32 20 247 S O 18 788 −24 19 247 S CB 47 803 −25 23 247 S OG 61 798 −23 30 248 T N 19 805 −39 18 248 T CA 5 808 −38 20 248 T C −4 797 −43 21 248 T O −15 795 −37 19 248 T CB 2 822 −45 25 248 T OG1 9 833 −38 22 248 T CG2 −13 825 −45 21 249 Y N −1 791 −55 17 249 Y CA −8 780 −61 16 249 Y C −9 768 −51 18 249 Y O −19 763 −48 20 249 Y CB −2 776 −74 17 249 Y CG −7 762 −80 20 249 Y CD1 −19 761 −87 22 249 Y CD2 0 750 −78 22 249 Y CE1 −23 748 −92 19 249 Y CE2 −4 738 −83 23 249 Y CZ −16 737 −90 30 249 Y OH −20 725 −95 45 250 M N 3 765 −45 13 250 M CA 3 754 −35 12 250 M C −5 756 −22 17 250 M O −13 748 −18 14 250 M CB 18 751 −30 14 250 M CG 27 745 −41 16 250 M SD 22 729 −47 18 250 M CE 24 717 −32 14 251 F N −4 768 −17 15 251 F CA −12 772 −5 16 251 F C −27 771 −7 18 251 F O −34 766 2 19 251 F CB −9 787 0 19 251 F CG 5 788 6 24 251 F CD1 12 800 6 28 251 F CD2 11 778 14 28 251 F CE1 24 802 12 30 251 F CE2 23 779 20 32 251 F CZ 30 791 20 30 252 K N −33 775 −18 15 252 K CA −47 773 −21 14 252 K C −51 758 −21 19 252 K O −62 755 −17 20 252 K CB −51 778 −35 15 252 K CG −51 794 −36 28 252 K CD −50 799 −50 33 252 K CE −52 814 −51 52 252 K NZ −53 820 −65 55 253 G N −43 749 −26 15 253 G CA −46 734 −26 13 253 G C −46 730 −11 17 253 G O −55 721 −7 16 254 I N −37 735 −3 14 254 I CA −36 731 12 15 254 I C −48 737 20 20 254 I O −52 731 30 21 254 I CB −22 738 17 19 254 I CG1 −10 729 14 19 254 I CG2 −23 740 33 22 254 I CD1 −12 714 17 27 255 I N −53 748 16 17 255 I CA −65 754 23 16 255 I C −78 746 19 22 255 I O −87 745 28 22 255 I CB −67 769 19 18 255 I CG1 −56 777 26 18 255 I CG2 −81 774 22 19 255 I CD1 −55 792 21 25 256 S N −79 742 7 17 256 S CA −90 733 3 16 256 S C −90 719 9 18 256 S O −100 714 13 18 256 S CB −91 732 −13 18 256 S OG −92 744 −20 26 257 F N −78 714 12 12 257 F CA −77 701 18 11 257 F C −83 702 33 19 257 F O −91 693 36 18 257 F CB −61 697 20 12 257 F CG −59 685 29 11 257 F CD1 −60 672 24 13 257 F CD2 −53 687 41 11 257 F CE1 −57 661 32 14 257 F CE2 −50 676 50 14 257 F CZ −52 663 45 13 258 A N −78 711 40 18 258 A CA −83 714 54 20 258 A C −98 715 54 29 258 A O −105 708 62 28 258 A CB −77 727 59 21 259 K N −104 724 46 29 259 K CA −118 726 44 30 259 K C −127 714 42 36 259 K O −138 713 47 36 259 K CB −121 737 34 32 259 K CG −120 751 39 37 259 K CD −123 761 29 55 259 K CE −119 775 33 83 259 K NZ −123 778 47 100 260 V N −122 704 34 32 260 V CA −130 693 31 32 260 V C −130 683 43 37 260 V O −139 674 44 38 260 V CB −127 686 17 36 260 V CG1 −127 696 6 36 260 V CG2 −115 678 18 36 261 I N −121 684 52 31 261 I CA −120 675 64 30 261 I C −131 678 74 34 261 I O −131 689 80 33 261 I CB −106 675 71 31 261 I CG1 −95 670 62 30 261 I CG2 −107 667 84 31 261 I CD1 −82 672 67 35 262 S N −140 669 77 31 262 S CA −151 671 87 30 262 S C −146 675 101 38 262 S O −152 684 107 36 262 S CB −160 659 87 31 262 S OG −157 650 98 35 263 Y N −135 669 105 39 263 Y CA −129 673 118 41 263 Y C −125 687 119 41 263 Y O −126 694 129 43 263 Y CB −118 663 122 45 263 Y CG −121 648 119 51 263 Y CD1 −117 642 107 54 263 Y CD2 −126 640 129 53 263 Y CE1 −118 629 105 57 263 Y CE2 −129 627 127 55 263 Y CZ −124 621 115 66 263 Y OH −126 608 113 70 264 F N −120 693 108 33 264 F CA −115 707 107 31 264 F C −127 716 106 38 264 F O −129 726 114 35 264 F CB −106 709 95 30 264 F CG −100 723 95 29 264 F CD1 −89 726 103 30 264 F CD2 −105 733 86 28 264 F CE1 −83 739 102 29 264 F CE2 −99 745 85 30 264 F CZ −88 748 93 28 265 R N −136 713 96 40 265 R CA −148 721 94 42 265 R C −156 723 107 50 265 R O −163 733 108 49 265 R CB −157 714 83 44 265 R CG −155 718 69 59 265 R CD −167 714 61 76 265 R NE −167 700 56 92 265 R CZ −172 690 62 7 265 R NH1 −179 692 74 95 265 R NH2 −172 678 57 93 266 D N −155 714 116 48 266 D CA −162 714 128 47 266 D C −156 725 138 52 266 D O −164 730 146 51 266 D CB −163 700 135 49 266 D CG −175 693 130 53 266 D OD1 −185 699 124 50 266 D OD2 −176 680 132 60 267 L N −143 727 138 48 267 L CA −137 737 147 46 267 L C −144 751 145 48 267 L O −151 752 135 47 267 L CB −122 738 145 46 267 L CG −113 726 148 51 267 L CD1 −98 730 146 51 267 L CD2 −116 720 162 53 268 P N −140 760 153 45 268 P CA −145 774 152 44 268 P C −137 782 142 48 268 P O −125 780 142 47 268 P CB −144 780 166 46 268 P CG −143 767 175 49 268 P CD −142 755 166 45 269 I N −143 791 134 47 269 I CA −136 799 124 49 269 I C −123 806 127 54 269 I O −116 809 118 54 269 I CB −146 809 117 52 269 I CG1 −143 811 102 53 269 I CG2 −145 822 124 53 269 I CD1 −138 798 95 60 270 E N −121 808 140 50 270 E CA −108 815 144 50 270 E C −97 805 147 50 270 E O −86 809 147 49 270 E CB −111 823 156 52 270 E CG −123 833 154 69 270 E CD −136 826 157 100 270 E OE1 −136 814 160 3 270 E OE2 −146 833 156 94 271 D N −101 792 150 43 271 D CA −91 782 152 42 271 D C −86 777 139 41 271 D O −75 773 137 42 271 D CB −97 771 161 44 271 D CG −98 775 176 51 271 D OD1 −100 766 184 50 271 D OD2 −96 787 179 54 272 Q N −95 777 129 34 272 Q CA −92 773 115 33 272 Q C −81 782 110 35 272 Q O −72 777 104 35 272 Q CB −105 775 106 35 272 Q CG −116 766 111 34 272 Q CD −127 765 100 42 272 Q OE1 −139 763 104 38 272 Q NE2 −124 767 88 36 273 I N −83 795 113 31 273 I CA −74 805 108 30 273 I C −60 804 114 32 273 I O −50 804 107 31 273 I CB −80 819 110 34 273 I CG1 −89 822 98 34 273 I CG2 −69 830 111 34 273 I CD1 −101 830 101 39 274 S N −60 803 127 28 274 S CA −47 801 135 28 274 S C −40 788 132 28 274 S O −28 788 132 25 274 S CB −50 801 150 32 274 S OG −56 814 155 41 275 L N −48 778 129 23 275 L CA −42 765 126 22 275 L C −36 765 112 25 275 L O −25 761 109 25 275 L CB −52 753 127 23 275 L CG −57 751 142 27 275 L CD1 −69 742 142 27 275 L CD2 −46 745 150 28 276 L N −43 772 102 20 276 L CA −38 773 88 21 276 L C −25 781 88 27 276 L O −16 778 81 26 276 L CB −49 778 79 20 276 L CG −59 767 73 25 276 L CD1 −72 772 67 24 276 L CD2 −53 756 63 27 277 K N −25 792 96 24 277 K CA −14 801 96 24 277 K C −1 794 101 27 277 K O 10 797 96 25 277 K CB −17 814 103 27 277 K CG −30 821 99 42 277 K CD −27 835 95 48 277 K CE −29 844 108 52 277 K NZ −38 856 105 56 278 G N −3 786 112 25 278 G CA 8 779 117 25 278 G C 14 767 109 30 278 G O 26 764 110 30 279 A N 5 760 101 27 279 A CA 9 748 94 26 279 A C 11 749 79 28 279 A O 17 739 73 26 279 A CB −1 737 98 26 280 A N 7 759 73 23 280 A CA 7 761 58 22 280 A C 21 758 51 25 280 A O 21 751 41 25 280 A CB 2 775 54 23 281 F N 32 762 57 21 281 F CA 46 759 52 20 281 F C 49 744 53 21 281 F O 54 738 44 19 281 F CB 56 768 60 22 281 F CG 70 763 58 23 281 F CD1 79 770 49 24 281 F CD2 76 753 65 24 281 F CE1 92 766 46 24 281 F CE2 89 749 63 26 281 F CZ 97 755 54 24 282 E N 46 739 65 16 282 E CA 48 724 67 14 282 E C 41 715 58 17 282 E O 46 705 53 17 282 E CB 46 721 82 15 282 E CG 53 731 92 18 282 E CD 50 729 107 34 282 E OE1 44 718 111 9 282 E OE2 54 738 115 22 283 L N 28 718 55 15 283 L CA 20 710 46 16 283 L C 26 710 32 18 283 L O 26 700 25 17 283 L CB 5 713 47 17 283 L CG −2 711 61 23 283 L CD1 −17 708 59 25 283 L CD2 5 701 70 24 284 C N 30 722 28 14 284 C N 30 722 28 11 284 C CA 35 725 15 14 284 C CA 35 724 15 10 284 C C 48 716 12 17 284 C C 48 716 12 15 284 C O 49 710 2 17 284 C O 50 711 1 15 284 C CB 39 739 13 15 284 C CB 38 739 12 10 284 C SG 43 744 −4 20 284 C SG 22 749 10 14 285 Q N 57 716 22 13 285 Q CA 69 708 21 14 285 Q C 67 693 21 18 285 Q O 74 685 14 19 285 Q CB 79 711 32 15 285 Q CG 83 726 33 16 285 Q CD 90 731 20 35 285 Q OE1 87 742 15 34 285 Q NE2 100 724 16 15 286 L N 56 688 29 11 286 L CA 53 673 29 10 286 L C 47 669 15 12 286 L O 51 659 9 10 286 L CB 42 670 40 10 286 L CG 47 672 55 15 286 L CD1 36 672 65 14 286 L CD2 58 662 59 12 287 R N 39 678 8 8 287 R CA 35 675 −6 7 287 R C 46 675 −16 10 287 R O 47 667 −25 7 287 R CB 24 685 −10 8 287 R CG 9 681 −5 9 287 R CD −2 690 −10 16 287 R NE −15 685 −7 12 287 R CZ −26 690 −11 19 287 R NH1 −27 700 −19 15 287 R NH2 −38 684 −7 8 288 F N 55 685 −15 9 288 F CA 67 685 −24 11 288 F C 76 673 −23 15 288 F O 83 670 −32 17 288 F CB 76 698 −22 14 288 F CG 71 710 −29 18 288 F CD1 70 723 −23 24 288 F CD2 69 710 −43 23 288 F CE1 66 734 −30 27 288 F CE2 65 721 −50 28 288 F CZ 63 733 −44 26 289 N N 77 668 −11 10 289 N CA 86 656 −9 11 289 N C 81 644 −17 16 289 N O 90 636 −22 16 289 N CB 87 652 6 15 289 N CG 98 641 8 24 289 N OD1 95 629 10 16 289 N ND2 110 645 6 6 290 T N 68 643 −20 14 290 T CA 63 632 −29 13 290 T C 66 633 −44 17 290 T O 66 623 −51 17 290 T CB 47 630 −27 19 290 T OG1 40 641 −33 15 290 T CG2 43 628 −12 15 291 V N 70 645 −49 15 291 V CA 75 647 −63 13 291 V C 90 648 −64 19 291 V O 96 651 −75 18 291 V CB 67 659 −70 16 291 V CG1 52 657 −70 14 291 V CG2 71 672 −64 15 292 F N 97 647 −52 16 292 F CA 112 648 −52 16 292 F C 119 635 −58 24 292 F O 115 624 −55 25 292 F CB 117 651 −38 17 292 F CG 132 653 −37 18 292 F CD1 138 663 −43 22 292 F CD2 140 645 −28 20 292 F CE1 152 666 −42 23 292 F CE2 153 647 −26 23 292 F CZ 159 658 −33 21 293 N N 129 637 −66 21 293 N CA 137 626 −71 22 293 N C 151 626 −65 29 293 N O 159 634 −68 25 293 N CB 138 625 −86 26 293 N CG 145 613 −92 43 293 N OD1 155 608 −86 39 293 N ND2 141 608 −103 26 294 A N 153 617 −55 30 294 A CA 165 617 −47 32 294 A C 177 613 −56 40 294 A O 189 616 −52 41 294 A CB 164 608 −35 33 295 E N 175 606 −67 38 295 E CA 186 602 −75 39 295 E C 192 614 −83 43 295 E O 204 614 −86 43 295 E CB 183 591 −84 41 295 E CG 173 581 −79 60 295 E CD 178 572 −68 0 295 E OE1 187 577 −60 4 295 E OE2 175 560 −67 6 296 T N 184 623 −87 37 296 T CA 189 634 −96 33 296 T C 188 648 −90 35 296 T O 190 658 −97 36 296 T CB 181 634 −109 36 296 T OG1 168 639 −107 31 296 T CG2 181 619 −114 36 297 G N 184 649 −77 27 297 G CA 182 662 −71 25 297 G C 173 671 −78 27 297 G O 175 682 −81 27 298 T N 161 665 −82 22 298 T CA 151 673 −89 21 298 T C 136 672 −84 23 298 T O 132 660 −82 24 298 T CB 151 671 −104 32 298 T OG1 146 659 −108 37 298 T CG2 166 672 −109 29 299 W N 129 683 −83 18 299 W CA 115 682 −80 17 299 W C 107 683 −93 20 299 W O 109 692 −101 18 299 W CB 111 694 −70 15 299 W CG 116 692 −56 17 299 W CD1 109 687 −45 20 299 W CD2 128 698 −50 17 299 W NE1 117 688 −33 18 299 W CE2 128 695 −36 20 299 W CE3 139 705 −56 19 299 W CZ2 139 699 −28 19 299 W CZ3 150 708 −48 20 299 W CH2 150 705 −34 21 300 E N 100 672 −97 19 300 E CA 93 671 −110 19 300 E C 79 674 −109 22 300 E O 71 666 −105 20 300 E CB 95 657 −115 21 300 E CG 109 651 −115 36 300 E CD 111 637 −119 68 300 E OE1 102 629 −116 75 300 E OE2 121 634 −125 70 301 C N 75 687 −114 17 301 C CA 62 692 −113 15 301 C C 54 692 −126 19 301 C O 51 703 −131 15 301 C CB 62 707 −107 14 301 C SG 71 708 −91 17 302 G N 50 680 −131 19 302 G CA 43 680 −143 20 302 G C 52 684 −155 25 302 G O 62 678 −158 23 303 R N 50 696 −161 24 303 R CA 58 701 −171 25 303 R C 70 710 −167 30 303 R O 78 713 −175 30 303 R CB 50 710 −181 27 303 R CG 38 704 −187 48 303 R CD 41 697 −200 65 303 R NE 29 692 −206 84 303 R CZ 29 682 −215 6 303 R NH1 40 678 −220 93 303 R NH2 17 678 −220 96 304 L N 71 714 −154 24 304 L CA 82 721 −149 24 304 L C 91 712 −141 27 304 L O 87 702 −136 30 304 L CB 78 733 −140 24 304 L CG 65 739 −143 30 304 L CD1 65 753 −136 30 304 L CD2 63 740 −157 36 305 S N 104 716 −139 23 305 S CA 113 709 −131 24 305 S C 123 719 −124 29 305 S O 126 729 −130 29 305 S CB 121 699 −139 27 305 S OG 113 691 −147 34 306 Y N 126 716 −112 24 306 Y CA 136 724 −105 23 306 Y C 148 715 −101 30 306 Y O 146 705 −94 29 306 Y CB 129 731 −92 24 306 Y CG 117 739 −95 25 306 Y CD1 104 734 −94 27 306 Y CD2 118 752 −100 25 306 Y CE1 93 742 −96 26 306 Y CE2 107 760 −103 26 306 Y CZ 94 755 −101 33 306 Y OH 83 762 −104 32 307 C N 159 718 −107 32 307 C CA 171 709 −105 35 307 C C 182 716 −97 38 307 C O 185 727 −99 34 307 C CB 176 706 −119 36 307 C SG 189 693 −121 40 308 L N 187 708 −87 40 308 L CA 197 714 −77 42 308 L C 210 717 −85 52 308 L O 214 710 −94 49 308 L CB 200 704 −66 42 308 L CG 194 707 −52 47 308 L CD1 194 721 −48 46 308 L CD2 180 701 −51 52 309 E N 215 729 −82 55 309 E CA 228 733 −89 59 309 E C 240 728 −81 71 309 E O 244 734 −71 71 309 E CB 228 749 −89 61 309 E CG 221 754 −102 70 309 E CD 226 749 −115 92 309 E OE1 229 737 −116 78 309 E OE2 228 757 −124 94 310 D N 246 717 −86 73 310 D CA 258 711 −79 75 310 D C 269 721 −78 83 310 D O 272 729 −87 83 310 D CB 262 699 −87 77 311 T N 276 721 −66 82 311 T CA 286 731 −63 83 311 T C 298 725 −55 89 311 T O 302 713 −57 89 311 T CB 281 743 −56 92 312 A N 304 733 −46 85 312 A CA 315 730 −38 85 312 A C 318 715 −34 88 312 A O 328 709 −39 87 312 A CB 316 739 −26 86 313 G N 310 710 −26 84 313 G CA 312 696 −21 84 313 G C 301 685 −23 89 313 G O 302 675 −17 89 314 G N 292 688 −32 85 314 G CA 282 679 −36 84 314 G C 272 675 −25 86 314 G O 268 684 −17 85 315 F N 267 663 −25 83 315 F CA 257 658 −15 83 315 F C 259 662 −1 87 315 F O 250 668 6 87 315 F CB 256 643 −16 85 316 Q N 271 659 5 82 316 Q CA 275 663 18 80 316 Q C 273 678 21 81 316 Q O 269 681 32 81 316 Q CB 290 659 21 81 317 Q N 277 686 12 75 317 Q CA 275 701 13 74 317 Q C 261 705 13 76 317 Q O 257 715 20 76 317 Q CB 283 708 2 75 318 L N 252 699 5 70 318 L CA 238 702 4 69 318 L C 230 697 16 70 318 L O 219 702 19 72 318 L CB 232 698 −10 69 318 L CG 241 699 −22 73 318 L CD1 234 694 −35 73 318 L CD2 246 713 −25 75 319 L N 235 686 22 62 319 L CA 227 680 33 60 319 L C 230 689 45 60 319 L O 223 688 55 60 319 L CB 232 666 36 60 319 L CG 232 657 23 64 319 L CD1 229 643 27 65 319 L CD2 221 662 14 67 320 L N 238 699 43 53 320 L CA 242 709 53 51 320 L C 230 719 55 53 320 L O 228 724 66 52 320 L CB 254 717 50 51 320 L CG 268 709 51 56 320 L CD1 278 717 59 56 320 L CD2 266 695 58 59 321 E N 224 722 44 46 321 E CA 212 731 44 44 321 E C 200 723 50 40 321 E O 197 713 44 40 321 E CB 209 736 30 45 321 E CG 197 745 28 59 321 E CD 197 756 38 83 321 E OE1 186 759 44 71 321 E OE2 207 763 40 79 322 P N 195 727 61 34 322 P CA 185 719 68 32 322 P C 173 714 60 33 322 P O 171 702 59 31 322 P CB 180 729 79 34 322 P CG 192 737 82 39 322 P CD 198 739 69 34 323 M N 167 723 52 29 323 M CA 156 720 43 29 323 M C 160 709 33 27 323 M O 152 701 29 25 323 M CB 151 732 36 34 323 M CG 137 731 30 41 323 M SD 124 730 43 49 323 M CE 122 712 45 45 324 L N 172 710 28 23 324 L CA 177 700 18 24 324 L C 180 687 24 27 324 L O 178 676 18 28 324 L CB 189 706 11 25 324 L CG 190 705 −4 33 324 L CD1 186 691 −9 34 324 L CD2 181 715 −11 38 325 K N 185 687 36 23 325 K CA 188 674 43 23 325 K C 175 667 47 25 325 K O 174 655 47 25 325 K CB 197 676 56 27 325 K CG 199 664 64 44 325 K CD 202 668 79 62 325 K CE 216 666 82 75 325 K NZ 219 667 97 85 326 F N 165 675 51 19 326 F CA 151 670 55 19 326 F C 145 662 43 22 326 F O 141 651 45 21 326 F CB 142 682 58 22 326 F CG 128 678 61 25 326 F CD1 124 673 74 28 326 F CD2 118 679 52 27 326 F CE1 111 669 77 28 326 F CE2 105 675 54 29 326 F CZ 101 670 67 27 327 H N 146 668 31 17 327 H CA 140 661 19 17 327 H C 147 648 16 21 327 H O 141 638 12 18 327 H CB 139 671 6 17 327 H CG 128 680 6 19 327 H ND1 115 677 1 20 327 H CD2 126 693 11 20 327 H CE1 107 687 2 20 327 H NE2 113 697 8 19 328 Y N 160 648 17 20 328 Y CA 168 635 15 21 328 Y C 164 624 25 23 328 Y O 161 613 22 22 328 Y CB 183 637 14 24 328 Y CG 188 641 0 27 328 Y CD1 191 654 −2 28 328 Y CD2 189 632 −10 28 328 Y CE1 195 658 −15 28 328 Y CE2 194 636 −23 29 328 Y CZ 197 649 −25 34 328 Y OH 201 653 −38 35 329 M N 165 628 38 20 329 M CA 161 619 49 23 329 M C 147 613 49 25 329 M O 145 601 51 25 329 M CB 165 625 63 27 329 M CG 180 627 65 34 329 M SD 183 637 81 42 329 M CE 175 626 93 39 330 L N 137 622 47 20 330 L CA 123 617 46 18 330 L C 121 607 34 23 330 L O 113 598 35 22 330 L CB 113 629 46 16 330 L CG 98 626 47 20 330 L CD1 94 619 60 20 330 L CD2 89 638 45 19 331 K N 127 610 22 21 331 K CA 125 602 10 21 331 K C 130 588 13 27 331 K O 125 578 9 28 331 K CB 131 609 −2 23 331 K CG 127 603 −16 20 331 K CD 113 607 −20 18 331 K CE 108 600 −33 21 331 K NZ 97 606 −41 18 332 K N 141 588 21 26 332 K CA 148 575 24 25 332 K C 139 565 32 27 332 K O 142 553 32 28 332 K CB 161 577 31 28 332 K CG 170 565 31 48 333 L N 129 570 39 23 333 L CA 121 562 47 21 333 L C 111 554 39 25 333 L O 104 545 44 24 333 L CB 114 569 58 21 333 L CG 122 578 68 25 333 L CD1 113 585 78 23 333 L CD2 133 571 74 28 334 Q N 109 558 26 23 334 Q CA 100 552 17 22 334 Q C 86 550 21 23 334 Q O 80 539 21 23 334 Q CB 106 539 12 24 334 Q CG 118 540 3 45 334 Q CD 123 527 −4 64 334 Q OE1 116 523 −13 64 334 Q NE2 133 521 2 44 335 L N 79 561 26 18 335 L CA 65 560 30 18 335 L C 55 558 20 21 335 L O 57 559 8 19 335 L CB 62 573 38 17 335 L CG 72 578 49 21 335 L CD1 67 591 55 20 335 L CD2 74 568 59 25 336 H N 43 554 24 18 336 H CA 31 552 15 17 336 H C 23 564 15 19 336 H O 24 573 24 18 336 H CB 22 541 22 19 336 H CG 29 527 23 23 336 H ND1 23 517 29 24 336 H CD2 41 523 18 24 336 H CE1 31 506 29 23 336 H NE2 42 510 22 24 337 E N 13 565 6 15 337 E CA 4 576 4 14 337 E C −3 578 18 16 337 E O −5 589 22 15 337 E CB −7 573 −6 16 337 E CG −2 572 −21 19 337 E CD 3 585 −27 22 337 E OE1 2 596 −20 19 337 E OE2 8 585 −38 15 338 E N −8 567 24 13 338 E CA −15 568 37 13 338 E C −7 574 49 17 338 E O −13 581 57 15 338 E CB −20 553 41 15 338 E CG −31 548 33 17 338 E CD −26 542 20 27 338 E OE1 −33 535 13 23 338 E OE2 −14 544 17 18 339 E N 6 571 49 13 339 E CA 15 576 60 13 339 E C 17 591 58 15 339 E O 17 599 67 13 339 E CB 28 568 61 14 339 E CG 24 553 65 15 339 E CD 36 543 62 31 339 E OE1 43 545 53 12 339 E OE2 35 533 69 24 340 Y N 19 596 45 10 340 Y CA 21 610 42 9 340 Y C 8 618 47 12 340 Y O 9 629 52 14 340 Y CB 24 613 27 10 340 Y CG 38 612 23 9 340 Y CD1 43 601 16 10 340 Y CD2 47 623 25 10 340 Y CE1 56 600 12 11 340 Y CE2 61 622 21 10 340 Y CZ 65 611 14 19 340 Y OH 78 610 10 12 341 V N −4 613 43 9 341 V CA −16 620 47 9 341 V C −20 621 62 13 341 V O −25 632 66 13 341 V CB −28 615 38 15 341 V CG1 −36 603 45 13 341 V CG2 −38 627 36 16 342 L N −15 612 70 12 342 L CA −16 612 84 12 342 L C −5 622 90 15 342 L O −8 629 100 14 342 L CB −15 598 91 13 342 L CG −28 589 90 16 342 L CD1 −24 575 89 14 342 L CD2 −38 592 102 17 343 M N 7 623 85 12 343 M CA 17 633 89 10 343 M C 11 647 86 15 343 M O 12 656 95 14 343 M CB 29 631 80 11 343 M CG 38 620 84 14 343 M SD 54 619 74 20 343 M CE 64 633 82 16 344 Q N 4 649 75 13 344 Q CA −3 662 72 10 344 Q C −13 665 83 18 344 Q O −14 676 89 18 344 Q CB −10 662 58 10 344 Q CG 0 663 46 8 344 Q CD −6 663 32 21 344 Q OE1 1 659 23 16 344 Q NE2 −19 666 31 13 345 A N −22 655 87 14 345 A CA −32 658 98 14 345 A C −26 661 112 17 345 A O −31 670 119 17 345 A CB −43 647 99 14 346 I N −16 654 116 13 346 I CA −9 656 129 13 346 I C −3 671 129 17 346 I O −5 678 140 16 346 I CB 2 645 132 15 346 I CG1 −4 632 134 14 346 I CG2 11 650 143 16 346 I CD1 6 620 133 13 347 S N 3 675 119 14 347 S CA 9 689 118 13 347 S C −2 699 118 18 347 S O −1 710 124 16 347 S CB 17 690 105 15 347 S OG 20 704 102 20 348 L N −13 697 110 16 348 L CA −24 706 110 15 348 L C −32 709 123 21 348 L O −35 720 127 22 348 L CB −34 702 99 14 348 L CG −46 712 98 18 348 L CD1 −43 726 93 17 348 L CD2 −57 706 89 18 349 F N −35 698 130 19 349 F CA −42 698 143 20 349 F C −32 699 154 25 349 F O −30 690 162 25 349 F CB −50 685 144 22 349 F CG −62 685 135 23 349 F CD1 −62 677 124 26 349 F CD2 −74 693 138 27 349 F CE1 −73 677 115 27 349 F CE2 −85 692 129 29 349 F CZ −84 685 118 27 350 S N −24 710 155 24 350 S CA −13 711 164 25 350 S C −19 721 175 34 350 S O −21 732 173 34 350 S CB −1 718 158 28 350 S OG 9 708 155 39 351 P N −21 715 187 35 351 P CA −27 723 198 36 351 P C −18 735 203 46 351 P O −23 744 210 45 351 P CB −29 713 209 37 351 P CG −19 703 207 41 351 P CD −16 702 192 35 352 D N −5 735 199 46 352 D CA 4 745 204 47 352 D C 7 757 195 51 352 D O 17 764 198 50 352 D CB 16 739 210 50 352 D CG 23 729 201 69 352 D OD1 16 720 195 71 352 D OD2 35 730 200 80 353 R N −1 760 185 46 353 R CA 1 771 176 45 353 R C −5 784 183 52 353 R O −14 783 190 51 353 R CB −6 768 163 42 353 R CG −3 755 156 39 353 R CD 10 756 147 37 353 R NE 10 744 139 43 353 R CZ 22 738 134 51 353 R NH1 33 744 137 31 353 R NH2 21 727 127 27 354 P N 2 795 180 50 354 P CA −3 808 185 50 354 P C −17 812 182 54 354 P O −21 813 170 53 354 P CB 7 818 179 51 354 P CG 19 810 174 56 354 P CD 16 795 177 51 355 G N −25 814 192 49 355 G CA −39 819 192 49 355 G C −50 808 192 52 355 G O −62 811 191 51 356 V N −46 795 193 50 356 V CA −56 785 193 50 356 V C −65 786 205 56 356 V O −61 789 216 55 356 V CB −49 771 193 54 356 V CG1 −59 760 199 53 356 V CG2 −45 767 179 53 357 L N −78 784 203 53 357 L CA −88 785 215 53 357 L C −92 771 221 58 357 L O −92 769 233 57 357 L CB −100 793 211 53 357 L CG −98 808 208 58 357 L CD1 −112 814 204 58 357 L CD2 −92 815 219 61 358 Q N −96 762 212 55 358 Q CA −101 749 216 54 358 Q C −89 739 216 59 358 Q O −90 727 212 59 358 Q CB −110 743 205 56 358 Q CG −122 752 203 69 358 Q CD −132 751 215 89 358 Q OE1 −129 755 226 83 358 Q NE2 −143 744 212 85 359 H N −77 743 222 57 359 H CA −65 735 221 58 359 H C −67 722 229 57 359 H O −59 713 228 57 359 H CB −54 743 228 60 359 H CG −57 747 242 65 359 H ND1 −56 738 252 67 359 H CD2 −62 758 247 67 359 H CE1 −60 744 263 67 359 H NE2 −64 756 260 67 360 R N −79 720 236 52 360 R CA −82 708 243 50 360 R C −88 698 233 48 360 R O −86 686 235 46 360 R CB −90 710 255 53 360 R CG −95 698 262 77 360 R CD −84 691 270 3 360 R NE −78 680 263 24 360 R CZ −65 678 263 44 360 R NH1 −57 687 269 31 360 R NH2 −59 668 257 34 361 V N −96 703 224 45 361 V CA −102 695 213 44 361 V C −91 691 203 42 361 V O −89 680 199 41 361 V CB −113 703 206 49 361 V CG1 −122 694 198 49 361 V CG2 −120 711 216 49 362 V N −83 702 199 36 362 V CA −72 700 189 35 362 V C −63 689 194 35 362 V O −60 680 187 35 362 V CB −65 713 187 37 362 V CG1 −55 712 176 37 362 V CG2 −75 724 184 37 363 D N −59 690 207 32 363 D CA −49 681 213 33 363 D C −55 666 214 36 363 D O −47 657 212 38 363 D CB −46 685 227 36 363 D CG −36 676 234 49 363 D OD1 −24 678 232 51 363 D OD2 −40 668 243 55 364 Q N −68 665 216 30 364 Q CA −74 652 216 30 364 Q C −75 646 202 30 364 Q O −73 633 200 30 364 Q CB −87 652 223 32 364 Q CG −92 637 226 57 364 Q CD −81 627 226 77 364 Q OE1 −82 616 220 62 364 Q NE2 −70 630 234 80 365 L N −78 654 192 26 365 L CA −78 650 177 25 365 L C −64 646 173 26 365 L O −62 635 168 28 365 L CB −83 662 169 26 365 L CG −98 665 171 29 365 L CD1 −102 677 163 29 365 L CD2 −106 654 166 33 366 Q N −54 654 176 21 366 Q CA −40 651 173 21 366 Q C −37 637 178 25 366 Q O −31 628 171 24 366 Q CB −30 661 179 22 366 Q CG −17 662 171 29 366 Q CD −6 670 177 37 366 Q OE1 −4 669 190 26 366 Q NE2 2 677 170 31 367 E N −40 634 191 24 367 E CA −36 621 197 23 367 E C −43 609 190 23 367 E O −37 598 189 21 367 E CB −40 621 212 25 367 E CG −39 607 218 38 367 E CD −39 607 233 60 367 E OE1 −46 615 239 44 367 E OE2 −33 597 239 54 368 Q N −55 611 185 22 368 Q CA −62 601 177 23 368 Q C −56 598 164 27 368 Q O −55 586 159 27 368 Q CB −76 605 174 26 368 Q CG −86 607 185 56 368 Q CD −100 608 180 91 368 Q OE1 −103 616 171 88 368 Q NE2 −108 599 185 86 369 F N −51 609 157 21 369 F CA −44 607 144 19 369 F C −31 600 146 23 369 F O −27 591 139 24 369 F CB −42 621 137 18 369 F CG −54 627 131 18 369 F CD1 −59 639 136 21 369 F CD2 −62 620 122 21 369 F CE1 −70 644 131 22 369 F CE2 −74 625 117 24 369 F CZ −78 637 122 21 370 A N −24 604 157 19 370 A CA −11 598 161 20 370 A C −13 582 164 24 370 A O −5 574 159 23 370 A CB −5 604 173 22 371 I N −23 579 171 22 371 I CA −26 565 174 21 371 I C −30 557 162 24 371 I O −25 545 160 21 371 I CB −37 563 185 25 371 I CG1 −31 566 199 26 371 I CG2 −44 549 185 24 371 I CD1 −42 571 209 29 372 T N −38 562 153 22 372 T CA −41 556 140 21 372 T C −28 553 132 24 372 T O −26 542 127 24 372 T CB −51 564 132 27 372 T OG1 −64 565 139 22 372 T CG2 −54 558 118 19 373 L N −19 563 131 20 373 L CA −6 560 124 19 373 L C 2 549 130 22 373 L O 5 539 123 20 373 L CB 2 573 124 19 373 L CG 16 572 117 23 373 L CD1 15 567 102 22 373 L CD2 23 586 117 22 374 K N 5 550 143 20 374 K CA 12 539 150 20 374 K C 6 525 147 26 374 K O 14 515 146 25 374 K CB 11 542 165 23 374 K CG 19 532 174 28 374 K CD 20 537 188 32 374 K CE 31 531 196 38 374 K NZ 27 519 203 41 375 S N −7 524 147 24 375 S CA −14 512 144 25 375 S C −13 507 129 30 375 S O −12 495 127 31 375 S CB −29 513 148 30 375 S OG −31 507 160 42 376 Y N −14 516 120 26 376 Y CA −12 512 105 25 376 Y C 1 506 104 25 376 Y O 3 495 98 20 376 Y CB −13 525 96 26 376 Y CG −11 522 81 26 376 Y CD1 2 522 76 27 376 Y CD2 −21 520 73 27 376 Y CE1 5 520 63 27 376 Y CE2 −19 518 59 27 376 Y CZ −6 518 54 31 376 Y OH −4 516 41 34 377 I N 12 513 108 23 377 I CA 26 508 107 23 377 I C 27 494 113 29 377 I O 33 486 107 28 377 I CB 36 518 114 25 377 I CG1 39 531 106 24 377 I CG2 48 510 118 23 377 I CD1 44 543 114 19 378 E N 21 492 124 29 378 E CA 21 479 131 32 378 E C 13 469 124 43 378 E O 17 457 125 44 378 E CB 15 481 145 34 378 E CG 26 483 156 44 378 E CD 19 488 169 67 378 E OE1 8 483 173 55 378 E OE2 26 496 177 60 379 C N 3 472 116 43 379 C CA −4 462 108 45 379 C C 2 459 95 47 379 C O 0 448 90 44 379 C CB −19 467 107 47 379 C SG −30 464 121 52 380 N N 9 468 88 44 380 N CA 14 466 75 43 380 N C 29 465 72 49 380 N O 34 461 62 49 380 N CB 7 476 65 43 380 N CG −7 479 69 77 380 N OD1 −16 470 68 72 380 N ND2 −10 491 73 75 381 R N 37 470 82 45 381 R CA 51 471 80 46 381 R C 59 463 91 53 381 R O 64 468 101 53 381 R CB 56 486 79 45 381 R CG 46 495 71 49 381 R CD 52 508 66 49 381 R NE 64 506 58 41 381 R CZ 69 514 49 57 381 R NH1 63 526 48 42 381 R NH2 80 511 43 54 382 P N 61 450 88 50 382 P CA 68 441 97 50 382 P C 83 438 95 51 382 P O 88 431 103 50 382 P CB 60 428 94 51 382 P CG 58 429 79 55 382 P CD 54 443 77 50 383 Q N 88 444 85 47 383 Q CA 103 442 82 47 383 Q C 111 450 92 52 383 Q O 108 461 97 51 383 Q CB 106 447 68 48 383 Q CG 98 441 57 67 383 Q CD 83 444 58 92 383 Q OE1 79 456 59 87 383 Q NE2 74 434 58 86 384 P N 123 444 95 50 384 P CA 132 450 105 49 384 P C 138 463 101 52 384 P O 145 470 108 52 384 P CB 143 440 105 51 384 P CG 136 427 103 56 384 P CD 124 430 94 51 385 A N 135 468 88 46 385 A CA 140 481 84 45 385 A C 130 491 88 46 385 A O 132 503 88 48 385 A CB 142 481 69 46 386 H N 118 486 93 38 386 H CA 107 494 98 35 386 H C 106 494 113 32 386 H O 95 499 118 30 386 H CB 94 492 89 36 386 H CG 97 492 74 40 386 H ND1 95 480 66 42 386 H CD2 103 501 66 41 386 H CE1 99 483 54 41 386 H NE2 103 495 53 41 387 R N 116 490 120 24 387 R CA 116 490 135 23 387 R C 118 505 139 25 387 R O 127 511 134 25 387 R CB 127 481 141 21 387 R CG 123 466 143 16 387 R CD 135 457 147 18 387 R NE 137 458 162 11 387 R CZ 147 452 169 23 387 R NH1 156 446 163 12 387 R NH2 147 453 182 17 388 F N 110 510 148 19 388 F CA 110 524 153 19 388 F C 106 534 142 22 388 F O 107 546 144 21 388 F CB 124 527 159 20 388 F CG 130 517 167 20 388 F CD1 143 511 164 21 388 F CD2 125 513 180 21 388 F CE1 149 501 172 20 388 F CE2 131 503 188 22 388 F CZ 142 497 184 18 389 L N 99 530 131 19 389 L CA 94 539 121 18 389 L C 85 550 126 21 389 L O 86 562 123 23 389 L CB 89 532 109 18 389 L CG 83 541 97 22 389 L CD1 94 549 90 21 389 L CD2 75 532 87 23 390 F N 76 546 135 14 390 F CA 66 556 141 13 390 F C 74 567 149 19 390 F O 70 578 148 20 390 F CB 55 549 149 13 390 F CG 47 558 157 13 390 F CD1 37 566 151 16 390 F CD2 49 560 171 13 390 F CE1 29 575 158 16 390 F CE2 42 570 178 16 390 F CZ 32 577 172 14 391 L N 85 563 156 18 391 L CA 93 573 164 17 391 L C 102 581 154 18 391 L O 105 593 157 19 391 L CB 101 567 175 17 391 L CG 93 561 187 22 391 L CD1 103 553 196 22 391 L CD2 86 571 195 19 392 K N 107 575 144 17 392 K CA 115 583 134 18 392 K C 106 594 127 24 392 K O 111 605 125 26 392 K CB 120 574 123 17 392 K CG 131 564 128 21 392 K CD 137 557 116 24 392 K CE 145 544 121 26 392 K NZ 150 535 110 30 393 I N 93 590 124 18 393 I CA 84 600 117 16 393 I C 81 612 126 17 393 I O 80 623 122 15 393 I CB 71 593 113 19 393 I CG1 73 583 101 17 393 I CG2 60 603 110 19 393 I CD1 61 575 97 14 394 M N 78 609 139 16 394 M CA 75 620 149 16 394 M C 87 629 151 19 394 M O 86 641 152 18 394 M CB 70 614 162 18 394 M CG 57 605 161 21 394 M SD 42 614 155 25 394 M CE 40 626 168 22 395 A N 99 623 151 14 395 A CA 112 631 152 16 395 A C 114 640 140 21 395 A O 119 652 141 18 395 A CB 124 622 153 17 396 M N 110 636 128 20 396 M CA 110 644 115 19 396 M C 100 655 116 21 396 M O 103 667 111 22 396 M CB 108 636 103 22 396 M CG 118 625 100 26 396 M SD 134 633 96 32 396 M CE 134 633 78 29 397 L N 88 653 122 15 397 L CA 78 663 123 15 397 L C 83 674 133 18 397 L O 79 685 132 15 397 L CB 65 657 128 15 397 L CG 55 651 117 19 397 L CD1 42 647 124 18 397 L CD2 53 661 105 16 398 T N 91 670 143 15 398 T CA 96 679 153 15 398 T C 106 689 146 22 398 T O 106 701 148 24 398 T CB 102 672 165 24 398 T OG1 91 667 173 18 398 T CG2 109 682 174 25 399 E N 115 683 138 20 399 E CA 125 690 130 18 399 E C 118 700 120 23 399 E O 123 711 118 23 399 E CB 135 681 123 19 399 E CG 143 688 113 31 399 E CD 156 693 119 49 399 E OE1 157 693 132 31 399 E OE2 165 697 112 39 400 L N 108 695 114 18 400 L CA 101 704 104 16 400 L C 95 717 110 17 400 L O 94 727 103 15 400 L CB 89 696 96 16 400 L CG 82 703 85 18 400 L CD1 91 707 74 17 400 L CD2 72 693 80 17 401 R N 90 715 122 17 401 R CA 85 727 129 17 401 R C 96 737 132 24 401 R O 93 749 132 24 401 R CB 79 722 142 19 401 R CG 71 732 150 35 401 R CD 63 726 162 52 401 R NE 57 736 170 49 401 R CZ 45 736 174 54 401 R NH1 37 726 171 45 401 R NH2 40 746 182 40 402 S N 108 732 135 22 402 S CA 119 741 138 22 402 S C 125 747 125 28 402 S O 129 759 125 26 402 S CB 130 733 145 27 402 S OG 143 739 142 41 403 I N 124 740 113 26 403 I CA 128 746 100 24 403 I C 117 757 96 27 403 I O 121 767 89 23 403 I CB 129 736 89 26 403 I CG1 141 726 92 25 403 I CG2 131 742 76 26 403 I CD1 141 714 84 20 404 N N 105 754 99 24 404 N CA 93 763 97 24 404 N C 96 777 103 32 404 N O 95 788 97 32 404 N CB 80 757 102 20 404 N CG 68 766 100 39 404 N OD1 68 776 93 27 404 N ND2 57 761 105 32 405 A N 99 777 116 31 405 A CA 102 789 124 32 405 A C 114 797 118 40 405 A O 114 809 117 40 405 A CB 104 787 138 33 406 Q N 124 790 113 39 406 Q CA 136 796 107 40 406 Q C 133 802 94 45 406 Q O 138 813 91 44 406 Q CB 147 786 107 42 406 Q CG 153 783 121 78 406 Q CD 158 795 128 15 406 Q OE1 154 797 140 11 406 Q NE2 166 803 121 15 407 H N 126 795 85 43 407 H CA 124 799 71 44 407 H C 114 811 72 42 407 H O 116 821 65 41 407 H CB 119 788 62 47 407 H CG 129 778 59 54 407 H ND1 133 775 46 58 407 H CD2 137 770 67 58 407 H CE1 143 765 47 58 407 H NE2 145 762 59 59 408 T N 105 811 81 36 408 T CA 95 822 83 36 408 T C 102 835 86 39 408 T O 98 846 81 36 408 T CB 84 819 93 46 408 T OG1 75 809 87 49 408 T CG2 76 832 96 42 409 Q N 112 835 94 36 409 Q CA 121 847 97 35 409 Q C 130 851 86 36 409 Q O 132 863 84 34 409 Q CB 129 845 110 37 409 Q CG 121 841 122 64 409 Q CD 111 852 126 2 409 Q OE1 113 864 123 1 409 Q NE2 100 848 132 1 410 R N 135 841 78 33 410 R CA 142 844 66 34 410 R C 133 853 56 38 410 R O 136 865 54 35 410 R CB 147 831 59 40 410 R CG 159 833 49 58 410 R CD 162 819 43 82 410 R NE 170 810 52 7 410 R CZ 176 799 49 28 410 R NH1 175 794 37 15 410 R NH2 183 792 58 21 411 L N 122 847 52 35 411 L CA 112 854 44 36 411 L C 109 868 49 35 411 L O 108 878 41 31 411 L CB 99 846 43 38 411 L CG 87 850 34 46 411 L CD1 85 839 23 48 411 L CD2 74 852 42 51 412 L N 106 869 62 32 412 L CA 102 882 67 31 412 L C 113 893 66 35 412 L O 110 905 63 32 412 L CB 98 881 82 32 412 L CG 83 877 84 37 412 L CD1 79 879 98 36 412 L CD2 75 886 75 43 413 R N 126 889 68 32 413 R CA 137 898 66 32 413 R C 138 902 51 37 413 R O 141 913 47 38 413 R CB 151 892 70 32 413 R CG 153 891 86 37 413 R CD 167 886 89 42 413 R NE 168 872 91 55 413 R CZ 174 864 82 72 413 R NH1 178 869 70 59 413 R NH2 174 851 84 56 414 I N 137 892 42 34 414 I CA 137 895 28 34 414 I C 126 905 24 42 414 I O 128 916 19 40 414 I CB 137 883 18 36 414 I CG1 150 875 19 35 414 I CG2 134 888 4 35 414 I CD1 149 860 15 29 415 Q N 113 901 27 41 415 Q CA 102 909 23 42 415 Q C 104 924 29 51 415 Q O 101 933 22 50 415 Q CB 89 904 29 42 415 Q CG 77 914 30 28 415 Q CD 70 915 16 34 415 Q OE1 73 908 7 31 415 Q NE2 61 925 15 20 416 D N 109 925 41 52 416 D CA 111 938 46 53 416 D C 120 947 37 58 416 D O 119 959 38 55 416 D CB 116 937 60 56 416 D CG 116 950 67 73 416 D OD1 123 960 63 74 416 D OD2 108 952 77 81 417 I N 129 940 30 55 417 I CA 139 948 21 54 417 I C 135 948 7 55 417 I O 138 957 −1 55 417 I CB 153 942 22 57 417 I CG1 160 945 36 58 417 I CG2 162 948 11 58 417 I CD1 171 936 39 69 418 H N 128 937 2 50 418 H CA 124 936 −12 48 418 H C 111 928 −13 48 418 H O 111 915 −13 48 418 H CB 135 929 −20 49 418 H CG 132 928 −34 52 418 H ND1 124 918 −40 54 418 H CD2 137 936 −45 53 418 H CE1 123 920 −53 53 418 H NE2 131 931 −56 53 419 P N 100 935 −13 43 419 P CA 86 930 −13 41 419 P C 84 921 −25 43 419 P O 87 925 −36 44 419 P CB 78 943 −15 42 419 P CG 86 954 −9 46 419 P CD 100 950 −11 42 420 F N 78 910 −22 35 420 F CA 75 900 −32 31 420 F C 62 893 −28 31 420 F O 54 888 −37 30 420 F CB 86 890 −34 30 420 F CG 89 883 −21 28 420 F CD1 84 870 −18 28 420 F CD2 98 889 −11 28 420 F CE1 87 864 −6 28 420 F CE2 100 883 1 30 420 F CZ 95 870 4 27 421 A N 59 893 −15 24 421 A CA 47 886 −10 23 421 A C 34 889 −18 25 421 A O 29 901 −18 25 421 A CB 45 888 5 23 422 T N 27 879 −23 18 422 T CA 14 881 −28 16 422 T C 3 885 −17 19 422 T O 6 883 −5 16 422 T CB 9 869 −36 19 422 T OG1 7 859 −26 21 422 T CG2 19 865 −46 18 423 P N −9 889 −22 19 423 P CA −19 891 −12 19 423 P C −23 879 −2 23 423 P O −24 881 10 24 423 P CB −31 896 −20 20 423 P CG −25 903 −31 24 423 P CD −11 896 −34 19 424 L N −24 867 −8 20 424 L CA −26 855 0 18 424 L C −14 853 10 24 424 L O −17 851 22 24 424 L CB −29 843 −8 18 424 L CG −32 829 −1 23 424 L CD1 −43 831 10 22 424 L CD2 −36 818 −11 24 425 M N −2 855 6 20 425 M CA 9 853 15 19 425 M C 9 863 26 24 425 M O 12 860 38 23 425 M CB 23 853 8 21 425 M CG 24 843 −4 25 425 M SD 39 844 −15 27 425 M CE 52 842 −2 25 426 Q N 5 875 23 22 426 Q CA 4 886 32 22 426 Q C −6 882 43 28 426 Q O −5 885 55 26 426 Q CB 0 899 26 24 426 Q CG 11 907 19 18 426 Q CD 6 919 10 30 426 Q OE1 −1 928 15 22 426 Q NE2 9 919 −3 18 427 E N −17 875 39 30 427 E CA −27 870 49 32 427 E C −22 860 58 40 427 E O −23 861 70 38 427 E CB −39 865 41 33 427 E CG −49 875 37 44 427 E CD −58 878 49 68 427 E OE1 −61 890 50 34 427 E OE2 −63 869 56 74 428 L N −16 849 52 38 428 L CA −11 838 60 39 428 L C 1 844 69 47 428 L O 0 843 81 43 428 L CB −5 827 51 39 428 L CG −16 821 42 42 428 L CD1 −9 811 32 42 428 L CD2 −26 814 51 40 429 F N 11 849 63 50 429 F CA 22 854 71 53 429 F C 19 866 80 57 429 F O 27 872 87 56 429 F CB 35 856 63 57 429 F CG 41 843 58 61 429 F CD1 37 837 46 66 429 F CD2 51 836 66 65 429 F CE1 43 825 42 68 429 F CE2 56 824 61 69 429 F CZ 52 818 49 67 430 G N 6 869 80 54 430 G CA 0 879 89 53 430 G C 1 894 85 57 430 G O −5 903 91 56 431 I N 9 897 74 54 431 I CA 11 911 70 53 431 I C −2 918 68 59 431 I O −12 912 62 58 431 I CB 20 912 57 56 431 I CG1 34 908 61 55 431 I CG2 20 926 53 56 431 I CD1 44 911 50 56 432 T N −3 930 71 57 432 T CA −15 938 71 57 432 T C −17 949 61 63 432 T O −28 955 60 60 432 T CB −18 945 85 69 432 T OG1 −14 959 85 64 432 T CG2 −10 938 96 70 433 G N −8 950 51 62 433 G CA −10 960 41 63 433 G C −8 974 46 71 433 G O −10 984 38 70 434 S N −4 976 58 70 434 S CA −1 989 63 69 434 S C 13 990 70 74 434 S O 17 982 78 73 434 S CB −12 993 73 73 434 S OG −18 1005 69 77

TABLE 4b Crystal coordinates for crystal 2 The following table contains one line for each atom of the solvent molecules observed in the PXR-LBD-L10-SRC monomers tetragonal crystal form. The columns are: 1) residue number, 2) 1-letter amino acid code, 3) atom name, 4) x-coordinate multiplied by 10, 5) y-coordinate multiplied by 10, 6) z-coordinate multiplied by 10, and 7) B-factor. 1 O OW 656 599 200 58 1 O OW −7 612 1 11 3 O OW −10 721 −26 15 4 O OW −2 815 −84 19 5 O OW −32 737 −55 31 7 O OW 93 586 20 16 8 O OW 82 531 168 14 9 O OW −20 715 −56 28 10 O OW 31 781 84 25 11 O OW −77 911 40 25 12 O OW −19 741 128 27 13 O OW −55 937 73 26 14 O OW 95 880 −129 29 15 O OW 167 664 89 29 16 O OW 19 962 64 30 17 O OW 15 542 −13 20 18 O OW −73 868 0 53 19 O OW −13 651 213 30 20 O OW −209 677 −8 75 22 O OW 112 833 23 42 23 O OW 103 574 −10 28 24 O OW −86 778 −18 37 25 O OW −132 627 −95 38 27 O OW 157 436 136 23 28 O OW 9 583 213 53 29 O OW 42 896 −59 18 30 O OW 34 710 148 40 31 O OW 184 907 −192 52 32 O OW 93 491 161 19 33 O OW 202 699 109 55 34 O OW 101 606 184 20 35 O OW −140 478 152 37 36 O OW 2 707 −73 28 37 O OW 188 590 65 46 38 O OW 24 645 13 32 39 O OW 43 924 −10 31 40 O OW 95 457 118 44 41 O OW 69 517 148 24 42 O OW 269 649 42 62 43 O OW −7 860 191 61 44 O OW 92 829 −17 43 45 O OW 172 724 148 51 46 O OW −174 782 19 54 47 O OW 237 914 −92 47 48 O OW −110 470 192 64 49 O OW 11 628 −8 31 50 O OW −28 807 −82 34 51 O OW −81 925 65 25 52 O OW −28 538 −22 35 53 O OW −85 776 −60 37 54 O OW −147 523 61 43 55 O OW 225 851 56 80 56 O OW 82 539 −26 44 58 O OW 20 706 −162 28 59 O OW 3 630 217 39 60 O OW 9 514 249 65 61 O OW 14 740 −163 43 62 O OW 107 856 −115 25 63 O OW 0 842 −78 29 64 O OW 1 821 −111 35 65 O OW 142 592 −53 27 66 O OW 89 506 22 32 67 O OW 66 531 190 35 68 O OW 139 659 158 21 69 O OW −12 806 144 28 70 O OW −107 656 247 40 71 O OW 87 922 68 49 72 O OW 151 684 154 24 73 O OW −83 582 196 37 74 O OW 16 949 90 34 75 O OW 78 495 137 23 76 O OW 310 931 −57 56 78 O OW 174 600 −1 40 79 O OW 99 599 −78 46 80 O OW −120 587 −18 30 81 O OW −35 906 71 38 82 O OW 59 639 −103 38 83 O OW 36 908 111 53 85 O OW 39 776 146 56 86 O OW 174 687 85 34 88 O OW −111 577 4 40 89 O OW 113 529 63 30 90 O OW 115 560 −28 43 91 O OW 139 446 67 41 93 O OW 70 491 15 41 94 O OW −90 684 −144 64 95 O OW −37 781 225 44 96 O OW −79 838 144 41 97 O OW 83 759 −18 57 98 O OW −128 778 267 48 99 O OW −102 561 163 45 100 O OW −136 537 41 45 101 O OW −161 852 257 53 102 O OW −18 986 108 48 103 O OW 254 742 17 56 104 O OW 151 914 −173 57 105 O OW 131 756 24 35 106 O OW 43 654 −111 43 107 O OW 327 744 −98 40 108 O OW 70 772 137 63 109 O OW 57 474 131 38 110 O OW 111 630 187 45 111 O OW 84 771 −53 47 112 O OW 5 689 −179 41 113 O OW 154 807 16 47 114 O OW 87 448 138 36 115 O OW 93 622 −85 52 116 O OW 80 901 −129 38 117 O OW 104 567 −57 52 118 O OW −73 565 173 45 119 O OW 108 431 128 51 120 O OW 70 760 15 44 121 O OW −35 883 85 42 123 O OW −146 758 66 47 124 O OW −89 895 68 41 125 O OW −85 545 26 44 126 O OW 97 466 25 58 127 O OW 157 663 −150 43 128 O OW 155 873 113 58 129 O OW 30 874 −164 43 130 O OW −113 730 239 49 132 O OW 172 874 −152 42 134 O OW 203 739 −220 57 135 O OW 8 873 −104 46 136 O OW 115 915 99 49 137 O OW −200 610 −21 50 138 O OW −15 621 241 46 139 O OW 29 816 −183 52 140 O OW 185 717 −161 50 141 O OW −146 519 159 52 142 O OW −2 391 73 39 143 O OW −160 567 72 41 144 O OW 197 632 −233 48 145 O OW 134 527 42 48 146 O OW −17 867 119 50 147 O OW 83 927 −168 58 148 O OW −26 792 −115 42 149 O OW 108 814 −25 54 150 O OW −80 808 177 47 151 O OW 42 513 154 51 152 O OW 101 823 −225 51 153 O OW −79 809 −12 44 154 O OW 36 505 225 43 155 O OW 99 478 −25 67 156 O OW 110 723 170 50 157 O OW 165 768 71 37 158 O OW −67 461 71 64 159 O OW 109 743 −46 58 160 O OW 68 874 −167 36 161 O OW 231 838 173 59 162 O OW 103 988 11 50 163 O OW 51 698 127 48 164 O OW −165 615 −37 57 165 O OW −165 544 65 53 166 O OW 57 950 40 39 167 O OW 57 857 −182 52 168 O OW −25 671 271 81 169 O OW 31 954 −3 44 170 O OW −31 681 −213 59 171 O OW 69 899 −157 49 172 O OW 50 669 175 66 173 O OW 113 732 −21 50 174 O OW 36 964 47 54 175 O OW 64 878 −66 75 179 O OW 293 734 −14 88 180 O OW 30 810 62 68 181 O OW 212 860 84 64 182 O OW 105 663 −137 94 183 O OW −60 457 47 74 184 O OW −60 492 164 66 185 O OW 109 408 77 52 186 O OW 51 449 146 71 187 O OW 65 471 45 58

Example 11 Crystallographic Analysis of PXR-linker-SRC in Complex with SR-12813 (Crystal 3)

A crystal of PXR-LBD-L10-SRC (SEQ ID NO: 24) grown according to the procedure described above was incubated for 24 h after adding 0.2 μL of a 100 mM SR-12813 sock solution (in DMSO) to the crystallization drop. The final compound concentration in the drop was therefore approximately 10 mM since the equilibrated drop was approximately 2 μL. After incubation, the crystal was crystallized, cooled and diffraction data collected as described above. Data collection, reduction, and refinement statistics are set forth below:

Data Collection Statistics:

Resolution 100-2.2 Å No. of collected reflections 111611 No. of unique reflections (F >= 0) 41422 R-sym 0.056 Percent of theoretical (I/s >= 1) 98.2% Unit Cell a = 86.0 Å, b = 89.3 Å, c = 106.0 Å, α = β = γ = 90° Space Group P2₁2₁2₁ Asymmetric unit 2 molecules

Refinement Statistics:

Theoretical number of reflections 42234 Number of reflections in working set 39312 (93.1%) Number of reflections in test set 2082 (4.9%) Number of refined atoms (total) 4879 Number of solvent atoms 44 R-factor 0.232 R-free 0.279 RMSD bond length 0.011 Å RMSD bond angles 1.1°

TABLE 5a Crystal coordinates for crystalline complex of PXR-LBD-L10-SRC and SR12813 (crystal 3). The following table contains one line for each protein atom in the first of the two observed PXR-LBD-L10-SRC monomers complexed with SR12813 in the orthorhombic asymmetric unit. The columns are: 1) residue number, 2) 1-letter amino acid code, 3) atom name, 4) x-coordinate multiplied by 10, 5) y-coordinate multiplied by 10, 6) z- coordinate multiplied by 10, and 7) B-factor. 142 G N 27 195 595 68 142 G CA 32 184 587 67 142 G C 22 181 575 68 142 G O 10 185 575 67 143 L N 27 175 565 63 143 L CA 19 172 553 60 143 L C 14 157 553 65 143 L O 21 148 558 65 143 L CB 28 173 540 59 143 L CG 31 187 534 62 143 L CD1 46 188 532 61 143 L CD2 24 189 522 59 144 T N 2 155 548 60 144 T CA −3 141 548 60 144 T C 7 132 540 67 144 T O 14 137 531 69 144 T CB −17 140 542 67 144 T OG1 −16 138 528 60 144 T CG2 −25 153 545 66 145 E N 7 119 543 64 145 E CA 16 110 535 63 145 E C 13 111 520 65 145 E O 22 109 512 65 145 E CB 13 96 540 65 145 E CG 19 85 531 78 145 E CD 33 82 534 107 145 E OE1 38 70 531 119 145 E OE2 40 91 538 91 146 E N 1 113 516 58 146 E CA −2 114 502 60 146 E C 5 126 495 64 146 E O 9 126 483 64 146 E CB −17 114 498 61 146 E CG −19 106 486 77 146 E CD −20 91 490 113 146 E OE1 −28 88 499 109 146 E OE2 −11 83 486 107 147 Q N 6 137 503 57 147 Q CA 12 149 498 55 147 Q C 27 149 497 58 147 Q O 33 155 490 55 147 Q CB 8 161 507 55 147 Q CG −7 162 509 48 147 Q CD −11 174 518 48 147 Q OE1 −5 177 527 55 147 Q NE2 −22 180 514 40 148 R N 32 140 506 53 148 R CA 47 138 506 54 148 R C 51 130 494 59 148 R O 60 132 487 59 148 R CB 51 132 519 53 148 R CG 53 142 530 67 148 R CD 59 137 543 86 148 R NE 50 128 550 107 148 R CZ 51 126 563 127 148 R NH1 60 132 570 119 148 R NH2 42 118 569 114 149 M N 43 119 491 57 149 M CA 44 111 480 57 149 M C 43 119 467 56 149 M O 50 116 457 58 149 M CB 34 100 480 60 149 M CG 35 90 492 66 149 M SD 52 88 496 72 149 M CE 59 82 479 69 150 M N 32 127 466 49 150 M CA 29 135 455 49 150 M C 41 144 451 48 150 M O 44 146 439 45 150 M CB 18 144 458 51 150 M CG 12 152 446 55 150 M SD −3 161 450 59 150 M CE −16 150 443 55 151 I N 48 150 461 43 151 I CA 59 159 459 42 151 I C 71 151 455 49 151 I O 79 155 447 53 151 I CB 62 167 472 43 151 I CG1 50 176 475 43 151 I CG2 74 176 471 41 151 I CD1 53 185 488 39 152 R N 73 139 462 45 152 R CA 84 131 458 45 152 R C 84 127 444 46 152 R O 94 126 437 48 152 R CB 84 118 467 51 152 R CG 96 108 465 75 152 R CD 109 116 464 99 152 R NE 121 107 465 109 152 R CZ 129 106 476 111 152 R NH1 126 113 487 89 152 R NH2 139 97 476 80 153 E N 72 124 438 39 153 E CA 70 120 424 40 153 E C 75 132 415 44 153 E O 81 129 405 45 153 E CB 56 116 421 39 153 E CG 56 103 412 52 153 E CD 44 102 403 68 153 E OE1 35 109 405 58 153 E OE2 45 93 395 77 154 L N 70 144 418 39 154 L CA 72 155 410 37 154 L C 88 158 411 40 154 L O 94 162 401 41 154 L CB 65 168 416 36 154 L CG 52 172 410 40 154 L CD1 45 163 401 37 154 L CD2 42 177 421 40 155 M N 93 157 423 33 155 M CA 107 160 425 33 155 M C 116 149 418 43 155 M O 127 153 413 46 155 M CB 110 161 440 35 155 M CG 107 174 447 36 155 M SD 114 188 439 39 155 M CE 130 188 446 35 156 D N 112 137 418 41 156 D CA 118 126 410 40 156 D C 118 129 396 42 156 D O 128 128 389 46 156 D CB 110 113 413 42 156 D CG 117 101 407 59 156 D OD1 110 93 399 59 156 D OD2 129 99 409 63 157 A N 106 132 390 36 157 A CA 104 135 376 36 157 A C 113 147 372 38 157 A O 119 147 361 42 157 A CB 90 138 373 37 158 Q N 114 157 380 32 158 Q CA 122 169 377 31 158 Q C 137 165 376 33 158 Q O 144 168 367 36 158 Q CB 120 180 388 32 158 Q CG 127 194 385 42 158 Q CD 119 203 376 42 158 Q OE1 112 199 366 27 158 Q NE2 118 215 381 22 159 M N 141 158 386 31 159 M CA 156 154 387 32 159 M C 160 146 375 34 159 M O 171 148 370 31 159 M CB 160 148 400 33 159 M CG 159 133 400 38 159 M SD 174 123 393 40 159 M CE 167 110 401 37 160 K N 151 137 371 30 160 K CA 154 128 359 31 160 K C 154 135 346 37 160 K O 159 131 336 39 160 K CB 143 117 359 33 160 K CG 145 106 369 38 160 K CD 133 97 369 41 160 K CE 134 86 380 55 160 K NZ 147 85 387 56 161 T N 146 146 345 32 161 T CA 144 152 332 30 161 T C 148 167 330 36 161 T O 146 173 320 36 161 T CB 129 151 329 41 161 T OG1 122 160 337 36 161 T CG2 124 137 332 35 162 F N 153 173 341 34 162 F CA 158 187 340 34 162 F C 173 187 340 40 162 F O 179 184 350 38 162 F CB 152 196 351 33 162 F CG 156 210 350 34 162 F CD1 151 219 359 32 162 F CD2 162 215 338 36 162 F CE1 154 233 358 34 162 F CE2 165 229 337 35 162 F CZ 162 237 347 34 163 D N 179 190 328 40 163 D CA 194 191 327 39 163 D C 199 205 331 43 163 D O 200 213 322 40 163 D CB 197 189 312 42 163 D CG 212 187 310 50 163 D OD1 220 184 319 47 163 D OD2 216 186 298 44 164 T N 200 207 344 40 164 T CA 203 220 349 39 164 T C 216 226 344 45 164 T O 217 239 344 49 164 T CB 202 221 364 32 164 T OG1 212 212 369 40 164 T CG2 189 216 369 30 165 T N 226 218 341 40 165 T CA 238 222 336 39 165 T C 239 222 321 44 165 T O 250 223 315 46 165 T CB 250 214 341 46 165 T OG1 250 202 334 47 165 T CG2 248 211 356 47 166 F N 228 220 314 42 166 F CA 227 219 299 43 166 F C 239 211 293 51 166 F O 243 215 282 53 166 F CB 225 232 293 43 166 F CG 213 239 297 44 166 F CD1 203 242 287 45 166 F CD2 211 244 310 45 166 F CE1 192 249 291 46 166 F CE2 200 250 314 45 166 F CZ 190 253 304 42 167 S N 244 201 300 49 167 S CA 254 192 294 51 167 S C 251 184 282 56 167 S O 260 180 274 58 167 S CB 260 183 305 54 167 S OG 250 179 314 66 168 H N 238 182 279 54 168 H CA 234 175 267 54 168 H C 229 183 256 54 168 H O 223 179 247 54 168 H CB 224 164 271 57 168 H CG 229 154 280 62 168 H ND1 234 157 293 66 168 H CD2 231 140 279 65 168 H CE1 239 146 299 65 168 H NE2 237 136 291 65 169 F N 230 196 258 45 169 F CA 226 205 247 44 169 F C 238 207 238 53 169 F O 247 215 241 52 169 F CB 221 219 253 44 169 F CG 215 228 242 42 169 F CD1 207 223 232 42 169 F CD2 218 241 242 40 169 F CE1 202 231 222 43 169 F CE2 213 250 232 42 169 F CZ 205 244 222 41 170 K N 237 201 227 54 170 K CA 248 203 217 56 170 K C 242 202 203 62 170 K O 231 199 201 61 170 K CB 260 193 219 60 170 K CG 257 181 228 77 170 K CD 251 170 219 91 170 K CE 243 160 227 108 170 K NZ 231 156 219 118 171 N N 251 205 193 60 171 N CA 247 204 179 60 171 N C 236 215 176 63 171 N O 228 212 167 68 171 N CB 242 190 175 58 171 N CG 253 180 176 90 171 N OD1 250 168 177 87 171 N ND2 266 184 177 80 172 F N 237 226 183 53 172 F CA 227 236 181 51 172 F C 233 246 171 54 172 F O 245 248 170 53 172 F CB 223 243 194 50 172 F CG 235 246 202 50 172 F CD1 242 258 200 51 172 F CD2 240 238 212 49 172 F CE1 253 261 207 51 172 F CE2 251 241 220 50 172 F CZ 258 253 217 48 173 R N 224 253 163 47 173 R CA 228 263 154 46 173 R C 232 276 161 50 173 R O 228 278 173 47 173 R CB 217 266 144 43 173 R CG 211 253 137 43 173 R CD 200 257 128 41 173 R NE 187 253 134 55 173 R CZ 175 256 130 70 173 R NH1 174 263 118 63 173 R NH2 164 253 137 66 174 L N 239 284 155 49 174 L CA 243 297 160 50 174 L C 242 308 149 59 174 L O 240 304 137 60 174 L CB 258 297 165 50 174 L CG 261 291 178 55 174 L CD1 276 288 180 53 174 L CD2 256 300 190 54 175 P N 243 320 153 57 175 P CA 242 331 143 57 175 P C 254 330 135 64 175 P O 265 331 140 63 175 P CB 243 344 152 58 175 P CG 238 339 165 63 175 P CD 243 325 167 57 176 G N 251 328 122 63 176 G CA 261 326 111 64 176 G C 273 335 113 72 176 G O 272 346 119 70 177 V N 284 330 108 71 177 V CA 297 336 110 72 177 V C 303 342 98 79 177 V O 307 353 97 81 177 V CB 306 327 118 75 177 V CG1 308 314 109 75 177 V CG2 319 334 121 75 192 S N 19 438 −9 85 192 S CA 28 447 −3 85 192 S C 23 456 8 90 192 S O 30 460 17 89 192 S CB 36 455 −13 91 192 S OG 45 465 −6 102 193 R N 10 460 8 86 193 R CA 5 468 19 86 193 R C 1 460 31 90 193 R O −2 466 42 90 193 R CB −4 480 16 89 193 R CG −1 492 25 101 193 R CD 14 496 23 114 193 R NE 20 503 34 125 193 R CZ 32 509 33 141 193 R NH1 39 507 22 123 193 R NH2 37 516 43 135 194 E N O 447 30 86 194 E CA −4 439 41 85 194 E C 9 433 47 88 194 E O 13 436 59 88 194 E CB −12 427 36 87 194 E CG −19 419 46 99 194 E CD −18 404 43 126 194 E OE1 −8 400 38 131 194 E OE2 −28 397 46 120 195 E N 17 427 38 82 195 E CA 30 422 42 80 195 E C 38 433 48 81 195 E O 46 430 57 80 195 E CB 37 416 29 82 195 E CG 32 403 24 93 195 E CD 35 391 34 124 195 E OE1 41 394 44 120 195 E OE2 30 380 31 129 196 A N 34 445 45 76 196 A CA 41 457 52 75 196 A C 36 457 66 75 196 A O 44 457 75 73 196 A CB 37 470 45 76 197 A N 23 458 68 71 197 A CA 17 458 81 70 197 A C 23 446 89 73 197 A O 27 446 101 72 197 A CB 2 457 80 70 198 K N 23 434 82 69 198 K CA 28 422 88 68 198 K C 42 424 94 73 198 K O 44 422 106 73 198 K CB 28 411 77 69 198 K CG 15 403 75 69 198 K CD 18 389 70 71 198 K CE 5 382 66 83 198 K NZ 9 370 57 91 199 W N 51 427 85 69 199 W CA 65 430 89 70 199 W C 66 440 100 75 199 W O 75 439 108 76 199 W CB 73 434 76 68 199 W CG 79 423 68 69 199 W CD1 73 416 58 72 199 W CD2 91 417 71 69 199 W NE1 82 407 53 72 199 W CE2 94 407 61 74 199 W CE3 101 420 81 71 199 W CZ2 105 399 61 73 199 W CZ3 113 412 80 72 199 W CH2 115 402 71 73 200 S N 58 450 99 72 200 S CA 58 461 109 72 200 S C 55 456 123 72 200 S O 60 461 133 71 200 S CB 49 473 105 76 200 S OG 38 474 114 85 201 Q N 46 446 124 67 201 Q CA 42 440 137 65 201 Q C 53 430 142 68 201 Q O 55 429 154 67 201 Q CB 29 432 135 66 201 Q CG 23 427 148 72 201 Q CD 20 438 158 83 201 Q OE1 25 439 169 76 201 Q NE2 11 448 154 75 202 V N 59 423 133 65 202 V CA 70 414 136 64 202 V C 83 422 142 68 202 V O 89 418 152 64 202 V CB 74 405 125 68 202 V CG1 88 400 126 68 202 V CG2 64 393 124 67 203 R N 86 433 135 67 203 R CA 97 442 139 67 203 R C 96 445 154 73 203 R O 106 446 161 75 203 R CB 98 454 130 66 203 R CG 104 452 116 74 203 R CD 107 466 109 80 203 R NE 106 464 95 96 203 R CZ 99 472 87 121 203 R NH1 92 483 92 111 203 R NH2 98 470 74 112 204 K N 84 447 159 70 204 K CA 81 451 172 70 204 K C 81 439 182 75 204 K O 83 440 194 76 204 K CB 67 457 174 72 204 K CG 66 471 166 95 204 K CD 52 474 163 96 204 K CE 51 482 151 102 204 K NZ 37 482 145 102 205 D N 78 427 176 71 205 D CA 77 415 184 70 205 D C 90 410 190 74 205 D O 90 405 201 73 205 D CB 71 404 175 71 205 D CG 55 404 174 72 205 D OD1 49 410 183 70 205 D OD2 50 399 164 67 206 L N 101 412 183 71 206 L CA 114 407 187 72 206 L C 124 419 187 79 206 L O 134 419 180 79 206 L CB 119 397 177 72 206 L CG 115 399 162 77 206 L CD1 126 406 154 78 206 L CD2 111 386 156 77 207 C N 121 429 196 76 207 C CA 130 440 197 76 207 C C 132 444 211 77 207 C O 140 451 215 78 207 C CB 125 452 189 77 207 C SG 112 462 198 81 208 S N 123 438 219 71 208 S CA 122 440 234 71 208 S C 127 428 241 74 208 S O 129 429 254 73 208 S CB 108 444 238 75 208 S OG 99 436 230 86 209 L N 127 417 234 69 209 L CA 132 404 240 68 209 L C 146 401 235 71 209 L O 149 390 231 70 209 L CB 122 393 236 68 209 L CG 107 394 241 74 209 L CD1 98 390 230 74 209 L CD2 105 385 253 76 210 K N 154 412 233 65 210 K CA 167 411 227 64 210 K C 178 406 237 66 210 K O 180 412 248 65 210 K CB 171 424 221 66 210 K CG 169 424 205 70 210 K CD 173 438 199 80 210 K CE 187 438 195 74 210 K NZ 191 452 191 85 211 V N 185 395 234 60 211 V CA 196 391 242 59 211 V C 209 390 235 61 211 V O 210 388 222 59 211 V CB 193 377 248 63 211 V CG1 183 377 260 62 211 V CG2 189 367 237 62 212 S N 220 390 243 55 212 S CA 233 387 238 54 212 S C 238 373 243 56 212 S O 232 368 252 55 212 S CB 243 398 243 58 212 S OG 252 393 253 64 213 L N 247 367 236 53 213 L CA 250 353 238 53 213 L C 265 350 242 55 213 L O 274 354 233 54 213 L CB 246 345 226 54 213 L CG 248 330 227 58 213 L CD1 239 323 216 57 213 L CD2 262 326 224 64 214 Q N 267 344 253 50 214 Q CA 281 340 257 48 214 Q C 283 325 256 55 214 Q O 274 318 259 56 214 Q CB 285 345 270 48 214 Q CG 299 341 274 66 214 Q CD 304 348 286 70 214 Q OE1 308 360 285 65 214 Q NE2 306 341 297 45 215 L N 295 321 252 54 215 L CA 297 307 251 55 215 L C 311 303 257 58 215 L O 321 305 250 57 215 L CB 298 304 236 57 215 L CG 288 295 229 63 215 L CD1 292 281 233 62 215 L CD2 274 298 234 68 216 R N 311 297 269 54 216 R CA 324 293 275 54 216 R C 329 280 270 61 216 R O 323 269 272 61 216 R CB 324 295 290 50 216 R CG 321 309 295 64 216 R CD 316 310 309 62 216 R NE 303 303 311 64 216 R CZ 291 308 307 74 216 R NH1 291 318 299 53 216 R NH2 280 301 310 69 217 G N 341 280 264 60 217 G CA 348 268 259 60 217 G C 354 261 270 66 217 G O 358 267 280 64 218 E N 355 248 269 66 218 E CA 360 240 280 67 218 E C 375 244 284 71 218 E O 380 240 294 71 218 E CB 360 225 276 69 218 E CG 345 220 275 85 218 E CD 344 205 276 113 218 E OE1 347 198 266 121 218 E OE2 340 200 287 105 219 D N 381 251 275 67 219 D CA 395 255 276 64 219 D C 397 269 283 68 219 D O 408 272 287 67 219 D CB 402 256 263 66 219 D CG 394 264 253 72 219 D OD1 386 273 256 69 219 D OD2 396 262 240 82 220 G N 387 277 285 64 220 G CA 388 290 291 63 220 G C 385 301 281 65 220 G O 382 313 285 62 221 S N 384 298 268 60 221 S CA 380 307 257 59 221 S C 366 311 259 60 221 S O 358 303 265 60 221 S CB 382 301 244 61 221 S OG 373 291 240 68 222 V N 362 323 254 54 222 V CA 348 327 255 54 222 V C 345 334 241 56 222 V O 353 342 236 54 222 V CB 346 338 266 57 222 V CG1 332 342 267 56 222 V CG2 352 333 279 57 223 W N 333 330 236 54 223 W CA 328 336 224 54 223 W C 316 345 228 55 223 W O 310 341 238 55 223 W CB 324 326 214 55 223 W CG 334 321 205 57 223 W CD1 341 309 205 60 223 W CD2 339 328 193 57 223 W NE1 349 308 194 59 223 W CE2 348 320 187 61 223 W CE3 337 340 188 59 223 W CZ2 355 324 175 61 223 W CZ3 343 344 176 60 223 W CH2 353 336 170 61 224 N N 314 356 222 52 224 N CA 303 365 226 50 224 N C 296 370 213 57 224 N O 303 377 205 57 224 N CB 308 376 235 40 224 N CG 297 384 241 68 224 N OD1 294 395 236 69 224 N ND2 292 380 252 57 225 Y N 283 368 212 53 225 Y CA 276 373 201 53 225 Y C 267 385 205 60 225 Y O 259 383 214 62 225 Y CB 267 362 195 54 225 Y CG 257 367 183 56 225 Y CD1 262 367 170 57 225 Y CD2 244 371 186 56 225 Y CE1 254 371 160 56 225 Y CE2 236 376 176 57 225 Y CZ 241 376 163 66 225 Y OH 233 380 152 72 226 K N 268 396 199 59 226 K CA 260 408 202 60 226 K C 251 409 190 67 226 K O 256 409 179 66 226 K CB 268 420 204 62 226 K CG 261 432 209 85 226 K CD 270 441 218 95 226 K CE 265 455 219 109 226 K NZ 272 463 230 124 227 P N 238 409 192 66 227 P CA 229 410 180 66 227 P C 230 424 175 71 227 P O 236 433 181 70 227 P CB 215 408 187 66 227 P CG 216 412 201 71 227 P CD 231 412 205 66 228 P N 225 426 162 69 228 P CA 225 439 156 69 228 P C 214 448 161 77 228 P O 204 443 166 77 228 P CB 223 436 141 70 228 P CG 216 422 141 74 228 P CD 220 415 154 69 229 A N 215 461 158 77 229 A CA 204 471 162 77 229 A C 195 473 150 85 229 A O 199 478 140 87 229 A CB 210 484 167 78 230 D N 182 468 152 82 230 D CA 172 468 141 82 230 D C 175 478 129 87 230 D O 178 490 131 86 230 D CB 158 470 147 84 230 D CG 147 467 137 94 230 D OD1 150 463 126 93 230 D OD2 135 469 141 101 231 S N 174 472 117 85 231 S CA 176 480 105 85 231 S C 165 476 95 90 231 S O 154 471 98 90 231 S CB 190 476 99 88 231 S OG 199 486 103 97 232 G N 168 479 82 87 232 G CA 158 476 71 86 232 G C 150 463 71 89 232 G O 139 462 65 89 233 G N 155 452 78 85 233 G CA 147 440 78 84 233 G C 153 427 83 87 233 G O 154 425 95 87 234 K N 155 417 74 82 234 K CA 159 403 77 81 234 K C 168 401 89 83 234 K O 165 392 98 82 234 K CB 165 396 65 84 234 K CG 155 392 55 103 234 K CD 146 380 60 113 234 K CE 135 377 50 124 234 K NZ 123 371 56 129 235 E N 180 407 90 78 235 E CA 190 405 100 77 235 E C 184 403 115 78 235 E O 191 398 123 79 235 E CB 199 417 101 78 235 E CG 192 430 106 86 235 E CD 187 438 94 103 235 E OE1 192 437 83 94 235 E OE2 179 447 97 87 236 I N 172 408 117 72 236 I CA 166 406 131 70 236 I C 162 392 134 71 236 I O 156 389 145 70 236 I CB 154 416 133 73 236 I CG1 141 410 127 73 236 I CG2 157 430 128 71 236 I CD1 133 420 120 81 237 F N 164 383 124 65 237 F CA 160 369 126 64 237 F C 171 360 130 66 237 F O 169 348 133 66 237 F CB 154 364 112 66 237 F CG 141 371 108 68 237 F CD1 138 374 95 70 237 F CD2 132 374 118 70 237 F CE1 126 379 92 71 237 F CE2 119 380 114 72 237 F CZ 117 382 101 70 238 S N 183 365 130 61 238 S CA 196 358 132 60 238 S C 197 349 144 61 238 S O 205 340 145 58 238 S CB 208 368 132 64 238 S OG 209 375 145 67 239 L N 189 352 155 56 239 L CA 189 344 167 56 239 L C 178 334 167 57 239 L O 179 324 175 57 239 L CB 188 353 179 57 239 L CG 200 353 190 62 239 L CD1 212 347 184 62 239 L CD2 202 366 195 67 240 L N 168 335 159 52 240 L CA 157 326 158 51 240 L C 161 311 157 54 240 L O 156 303 165 56 240 L CB 146 330 148 51 240 L CG 140 343 151 55 240 L CD1 129 347 142 55 240 L CD2 135 344 166 55 241 P N 170 307 148 49 241 P CA 174 293 146 48 241 P C 180 287 159 51 241 P O 177 276 163 56 241 P CB 185 294 135 48 241 P CG 182 306 128 51 241 P CD 176 316 138 47 242 H N 188 295 166 46 242 H CA 194 290 178 45 242 H C 184 289 190 48 242 H O 184 279 197 46 242 H CB 205 300 183 45 242 H CG 211 297 196 49 242 H ND1 218 285 198 50 242 H CD2 211 303 208 50 242 H CE1 222 284 211 49 242 H NE2 217 295 217 50 243 M N 175 298 191 46 243 M CA 164 298 201 47 243 M C 155 287 199 48 243 M O 149 282 209 46 243 M CB 156 311 200 51 243 M CG 164 324 204 56 243 M SD 172 321 220 64 243 M CE 189 322 216 62 244 A N 152 283 186 42 244 A CA 143 272 183 38 244 A C 149 259 188 40 244 A O 142 250 193 38 244 A CB 141 271 167 40 245 D N 163 258 187 37 245 D CA 170 246 191 35 245 D C 170 245 207 38 245 D O 168 235 212 38 245 D CB 185 246 186 38 245 D CG 185 244 171 44 245 D OD1 176 238 166 37 245 D OD2 196 247 165 48 246 M N 173 256 213 35 246 M CA 172 256 228 34 246 M C 158 253 233 40 246 M O 157 246 242 41 246 M CB 177 269 234 35 246 M CG 174 269 250 37 246 M SD 184 257 258 40 246 M CE 199 267 263 35 247 S N 148 260 227 39 247 S CA 134 257 231 39 247 S C 130 243 229 43 247 S O 126 236 238 46 247 S CB 125 266 223 43 247 S OG 125 279 229 58 248 T N 132 238 217 37 248 T CA 129 224 213 36 248 T C 136 215 223 38 248 T O 130 206 228 40 248 T CB 135 222 199 42 248 T OG1 127 229 189 43 248 T CG2 136 207 196 43 249 Y N 149 218 227 33 249 Y CA 156 210 236 32 249 Y C 149 210 250 37 249 Y O 148 200 257 37 249 Y CB 171 216 238 34 249 Y CG 178 208 249 37 249 Y CD1 183 196 247 41 249 Y CD2 180 213 262 38 249 Y CE1 191 188 256 35 249 Y CE2 187 206 272 39 249 Y CZ 192 194 269 42 249 Y OH 199 187 278 55 250 M N 144 222 254 35 250 M CA 137 224 267 35 250 M C 123 216 266 41 250 M O 120 209 276 41 250 M CB 135 238 270 36 250 M CG 148 246 273 38 250 M SD 155 240 288 42 250 M CE 144 245 301 37 251 F N 116 218 255 37 251 F CA 103 211 254 37 251 F C 104 196 255 43 251 F O 96 189 262 46 251 F CB 96 214 240 39 251 F CG 93 228 238 40 251 F CD1 92 233 225 42 251 F CD2 90 236 248 40 251 F CE1 89 246 222 43 251 F CE2 86 250 246 42 251 F CZ 86 255 233 41 252 K N 114 189 248 37 252 K CA 116 175 250 36 252 K C 118 171 265 39 252 K O 114 160 269 41 252 K CB 127 170 242 40 252 K CG 127 174 227 46 252 K CD 139 169 220 59 252 K CE 142 154 223 80 252 K NZ 144 146 210 92 253 G N 124 179 272 34 253 G CA 126 176 286 32 253 G C 113 179 294 38 253 G O 112 172 305 38 254 I N 105 188 290 35 254 I CA 92 190 296 36 254 I C 82 179 293 39 254 I O 74 175 302 42 254 I CB 85 203 290 40 254 I CG1 93 216 293 41 254 I CG2 71 204 294 41 254 I CD1 98 216 306 49 255 I N 83 173 282 31 255 I CA 75 161 278 28 255 I C 79 149 286 36 255 I O 71 142 291 37 255 I CB 77 158 263 32 255 I CG1 71 170 254 28 255 I CG2 71 144 259 37 255 I CD1 73 169 240 31 256 S N 93 147 287 32 256 S CA 97 136 295 33 256 S C 92 137 309 38 256 S O 87 128 315 40 256 S CB 113 135 295 33 256 S OG 117 132 283 39 257 F N 92 149 315 36 257 F CA 88 152 328 34 257 F C 73 148 331 36 257 F O 70 142 341 38 257 F CB 89 167 331 34 257 F CG 82 172 343 35 257 F CD1 89 172 356 38 257 F CD2 70 179 342 37 257 F CE1 82 177 367 37 257 F CE2 64 184 354 37 257 F CZ 70 182 366 34 258 A N 64 152 322 33 258 A CA 50 149 323 35 258 A C 49 133 322 43 258 A O 42 127 330 44 258 A CB 43 155 311 35 259 K N 55 127 312 45 259 K CA 55 113 310 46 259 K C 58 105 323 50 259 K O 53 94 325 49 259 K CB 65 109 299 50 259 K CG 58 107 285 62 259 K CD 68 101 275 71 259 K CE 77 91 281 83 259 K NZ 89 89 273 95 260 V N 68 110 331 47 260 V CA 71 102 343 46 260 V C 61 103 355 50 260 V O 62 96 365 49 260 V CB 85 106 348 50 260 V CG1 93 114 339 50 260 V CG2 85 111 362 50 261 I N 51 112 353 48 261 I CA 41 114 364 47 261 I C 29 105 362 52 261 I O 22 105 352 51 261 I CB 36 129 364 50 261 I CG1 48 139 366 50 261 I CG2 25 132 375 48 261 I CD1 44 153 364 49 262 S N 27 96 372 48 262 S CA 16 87 371 49 262 S C 2 93 368 54 262 S O −5 89 359 53 262 S CB 15 79 384 55 262 S OG 14 87 396 69 263 Y N −1 104 375 51 263 Y CA −13 111 373 51 263 Y C −15 116 358 50 263 Y O −27 117 354 48 263 Y CB −14 123 382 54 263 Y CG −10 121 396 59 263 Y CD1 3 126 400 61 263 Y CD2 −18 115 405 61 263 Y CE1 7 124 413 63 263 Y CE2 −14 114 418 62 263 Y CZ −2 118 422 71 263 Y OH 2 116 435 78 264 F N −4 119 351 45 264 F CA −5 123 337 44 264 F C −6 111 328 52 264 F O −13 111 318 51 264 F CB 8 131 334 43 264 F CG 8 137 320 41 264 F CD1 1 149 317 43 264 F CD2 14 131 309 41 264 F CE1 1 154 305 44 264 F CE2 14 136 297 43 264 F CZ 8 148 294 40 265 R N 2 100 330 51 265 R CA 2 88 322 52 265 R C −13 83 322 57 265 R O −18 79 311 58 265 R CB 11 78 328 54 265 R CG 25 78 320 65 265 R CD 33 65 323 63 265 R NE 39 66 336 60 265 R CZ 33 61 347 76 265 R NH1 21 55 347 71 265 R NH2 40 62 359 59 266 D N −19 82 333 54 266 D CA −33 77 334 55 266 D C −43 84 326 62 266 D O −54 79 324 64 266 D CB −38 77 349 56 266 D CG −29 68 358 65 266 D OD1 −23 59 352 64 266 D OD2 −29 71 370 77 267 L N −40 96 321 58 267 L CA −49 103 312 57 267 L C −48 98 298 60 267 L O −38 92 294 60 267 L CB −46 118 312 57 267 L CG −48 127 325 62 267 L CD1 −43 141 322 62 267 L CD2 −63 127 329 60 268 P N −59 99 290 57 268 P CA −59 94 277 56 268 P C −50 102 268 61 268 P O −50 115 268 62 268 P CB −74 96 272 57 268 P CG −80 104 282 62 268 P CD −72 103 295 58 269 I N −42 96 259 59 269 I CA −32 102 250 59 269 I C −36 115 245 62 269 I O −28 124 243 62 269 I CB −28 92 239 63 269 I CG1 −15 97 232 64 269 I CG2 −39 92 228 63 269 I CD1 −3 97 241 69 270 E N −49 116 242 58 270 E CA −54 129 235 57 270 E CB −68 127 230 58 270 E C −53 140 245 58 270 E O −50 152 241 55 271 D N −56 137 258 53 271 D CA −56 147 268 53 271 D C −41 151 271 55 271 D O −38 162 273 57 271 D CB −63 142 281 55 271 D CG −78 145 281 66 271 D OD1 −84 141 291 65 271 D OD2 −83 150 270 76 272 Q N −33 141 272 49 272 Q CA −18 142 274 47 272 Q C −13 152 264 50 272 Q O −5 161 267 51 272 Q CB −11 129 273 49 272 Q CG −14 120 284 52 272 Q CD −6 107 283 66 272 Q OE1 −12 97 284 63 272 Q NE2 6 108 278 51 273 I N −17 151 251 46 273 I CA −13 160 240 46 273 I C −18 174 242 49 273 I O −11 184 241 50 273 I CB −18 155 227 49 273 I CG1 −11 142 223 49 273 I CG2 −16 166 216 49 273 I CD1 −15 137 209 44 274 S N −31 176 246 44 274 S CA −37 189 247 45 274 S C −31 197 259 45 274 S O −28 208 259 43 274 S CB −52 187 249 52 274 S OG −58 178 240 65 275 L N −29 189 270 40 275 L CA −22 195 282 39 275 L C −8 200 279 44 275 L O −4 211 284 44 275 L CB −22 185 293 37 275 L CG −36 182 299 39 275 L CD1 −34 175 312 37 275 L CD2 −44 195 301 40 276 L N −1 193 272 40 276 L CA 13 196 268 38 276 L C 14 208 258 44 276 L O 22 216 260 43 276 L CB 20 184 262 38 276 L CG 26 174 272 43 276 L CD1 31 162 265 46 276 L CD2 37 180 280 39 277 K N 5 208 249 42 277 K CA 4 219 239 43 277 K C 2 232 246 46 277 K O 7 242 242 45 277 K CB −7 216 229 45 277 K CG −5 205 219 38 277 K CD −17 204 209 46 277 K CE −21 218 204 51 277 K NZ −17 221 190 66 278 G N −8 232 256 43 278 G CA −11 244 263 40 278 G C −1 249 273 44 278 G O 1 261 275 43 279 A N 6 240 279 39 279 A CA 16 243 290 39 279 A C 31 243 286 43 279 A O 39 249 293 43 279 A CB 14 233 301 39 280 A N 34 237 275 40 280 A CA 48 237 270 39 280 A C 56 249 273 40 280 A O 67 250 279 39 280 A CB 50 232 256 40 281 F N 51 260 268 36 281 F CA 59 273 270 37 281 F C 60 277 284 41 281 F O 70 283 289 41 281 F CB 51 284 262 38 281 F CG 56 298 265 39 281 F CD1 65 304 257 39 281 F CD2 50 305 276 41 281 F CE1 69 318 260 39 281 F CE2 54 318 279 40 281 F CZ 63 324 271 38 282 E N 49 274 292 32 282 E CA 48 277 306 31 282 E C 58 270 314 36 282 E O 65 276 322 37 282 E CB 34 275 311 32 282 E CG 24 286 305 31 282 E CD 10 284 309 39 282 E OE1 7 279 320 33 282 E OE2 1 289 301 46 283 L N 60 257 313 35 283 L CA 69 249 321 35 283 L C 83 253 317 36 283 L O 92 253 326 36 283 L CB 68 234 318 35 283 L CG 54 229 322 41 283 L CD1 55 216 331 37 283 L CD2 45 239 329 41 284 C N 86 256 305 32 284 C CA 99 259 300 34 284 C C 104 272 306 36 284 C O 115 274 311 38 284 C CB 100 260 284 37 284 C SG 116 266 278 43 285 Q N 94 282 307 29 285 Q CA 98 295 313 31 285 Q C 100 293 328 33 285 Q O 108 300 335 35 285 Q CB 87 306 311 33 285 Q CG 86 310 296 29 285 Q CD 99 315 291 48 285 Q OE1 104 311 280 43 285 Q NE2 106 324 298 31 286 L N 92 284 334 29 286 L CA 93 281 349 30 286 L C 107 274 352 33 286 L O 114 278 361 34 286 L CB 82 272 354 30 286 L CG 68 279 355 34 286 L CD1 58 269 361 33 286 L CD2 70 291 365 34 287 R N 112 266 342 29 287 R CA 125 260 344 28 287 R C 136 270 342 34 287 R O 146 271 350 35 287 R CB 127 248 335 31 287 R CG 118 236 338 31 287 R CD 122 223 330 29 287 R NE 118 211 337 33 287 R CZ 120 198 334 44 287 R NH1 126 196 322 30 287 R NH2 115 189 341 26 288 F N 134 279 332 31 288 F CA 144 290 329 31 288 F C 145 299 341 34 288 F O 155 304 343 33 288 F CB 140 298 316 33 288 F CG 146 292 303 35 288 F CD1 138 292 292 39 288 F CD2 158 286 303 40 288 F CE1 143 286 280 42 288 F CE2 164 281 291 43 288 F CZ 156 281 280 41 289 N N 134 301 348 32 289 N CA 135 310 359 35 289 N C 145 305 369 37 289 N O 153 313 375 41 289 N CB 121 313 366 38 289 N CG 121 324 376 40 289 N OD1 122 322 388 38 289 N ND2 123 336 371 29 290 T N 146 292 371 32 290 T CA 155 286 380 30 290 T C 170 288 377 34 290 T O 178 287 386 34 290 T CB 153 271 383 35 290 T OG1 158 264 372 32 290 T CG2 138 268 385 31 291 V N 173 292 365 33 291 V CA 187 295 360 32 291 V C 189 310 358 36 291 V O 199 313 352 37 291 V CB 191 287 348 33 291 V CG1 190 272 351 33 291 V CG2 184 292 336 30 292 F N 179 318 361 32 292 F CA 180 332 358 32 292 F C 187 338 370 39 292 F O 184 335 382 39 292 F CB 166 338 357 34 292 F CG 166 353 354 35 292 F CD1 171 357 343 40 292 F CD2 159 362 363 35 292 F CE1 171 372 340 38 292 F CE2 159 375 360 36 292 F CZ 164 380 348 34 293 N N 196 347 367 37 293 N CA 204 355 377 36 293 N C 199 369 375 42 293 N O 202 376 366 42 293 N CB 219 355 374 39 293 N CG 228 362 383 55 293 N OD1 223 373 389 50 293 N ND2 240 357 386 47 294 A N 191 374 385 43 294 A CA 186 387 384 46 294 A C 196 398 388 52 294 A O 193 410 385 52 294 A CB 173 388 393 48 295 E N 208 395 393 52 295 E CA 217 406 396 54 295 E C 223 411 384 60 295 E O 226 422 382 62 295 E CB 229 400 405 56 295 E CG 226 388 414 77 295 E CD 218 392 426 107 295 E OE1 209 384 430 105 295 E OE2 221 403 432 106 296 T N 225 402 374 56 296 T CA 231 404 361 52 296 T C 221 403 349 54 296 T O 225 404 338 56 296 T CB 242 395 359 57 296 T OG1 238 382 356 62 296 T CG2 251 394 372 46 297 G N 208 400 352 49 297 G CA 199 398 341 47 297 G C 203 388 331 50 297 G O 202 389 319 48 298 T N 209 377 335 47 298 T CA 214 366 327 44 298 T C 208 352 330 48 298 T O 207 348 342 49 298 T CB 230 365 328 51 298 T OG1 236 377 325 53 298 T CG2 236 355 319 50 299 W N 204 345 320 42 299 W CA 200 331 322 43 299 W C 212 323 320 46 299 W O 218 323 309 45 299 W CB 189 327 311 42 299 W CG 175 333 314 43 299 W CD1 165 328 322 46 299 W CD2 170 345 309 44 299 W NE1 154 337 322 46 299 W CE2 157 347 314 48 299 W CE3 176 355 300 45 299 W CZ2 150 358 311 48 299 W CZ3 168 366 297 47 299 W CH2 155 368 302 48 300 E N 217 317 330 40 300 E CA 229 308 330 40 300 E C 227 294 327 41 300 E O 224 286 336 41 300 E CB 237 310 343 42 300 E CG 241 325 345 52 300 E CD 246 327 359 72 300 E OE1 248 317 367 77 300 E OE2 249 339 362 71 301 C N 229 290 315 38 301 C CA 226 276 310 38 301 C C 239 268 307 42 301 C O 242 265 295 41 301 C CB 218 277 297 36 301 C SG 203 287 299 39 302 G N 246 264 317 38 302 G CA 258 256 315 38 302 G C 269 265 309 46 302 G O 273 275 315 44 303 R N 274 261 298 46 303 R CA 284 269 291 47 303 R CB 293 260 281 51 303 R CG 301 249 289 62 303 R CD 311 255 299 80 303 R C 278 280 282 53 303 R O 286 288 277 53 304 L N 265 281 282 51 304 L CA 258 292 275 50 304 L C 252 302 285 53 304 L O 249 298 296 53 304 L CB 246 286 267 51 304 L CG 249 280 253 56 304 L CD1 240 268 250 55 304 L CD2 247 291 243 59 305 S N 251 314 280 50 305 S CA 245 325 289 48 305 S C 237 334 279 52 305 S O 241 335 268 51 305 S CB 255 333 295 50 305 S OG 262 325 305 61 306 Y N 226 339 284 50 306 Y CA 217 348 276 49 306 Y C 216 360 285 54 306 Y O 211 359 296 53 306 Y CB 204 342 273 50 306 Y CG 205 329 265 50 306 Y CD1 205 316 272 51 306 Y CD2 209 329 252 49 306 Y CE1 206 305 265 51 306 Y CE2 209 317 245 48 306 Y CZ 208 305 252 52 306 Y OH 210 293 245 45 307 C N 222 371 280 52 307 C CA 221 384 287 53 307 C C 213 394 280 59 307 C O 212 395 268 57 307 C CB 236 389 288 53 307 C SG 239 402 301 58 308 L N 205 401 288 60 308 L CA 196 412 283 61 308 L C 206 424 282 71 308 L O 215 425 290 70 308 L CB 185 415 294 60 308 L CG 172 409 296 62 308 L CD1 168 399 285 62 308 L CD2 170 403 309 60 309 E N 202 434 274 74 309 E CA 210 446 273 76 309 E C 203 458 280 84 309 E O 191 461 277 85 309 E CB 212 450 258 79 309 E CG 217 438 250 94 309 E CD 231 433 253 126 309 E OE1 233 422 259 117 309 E OE2 240 440 248 125 310 D N 210 466 288 84 310 D CA 204 478 294 85 310 D C 204 488 283 90 310 D O 213 489 274 90 310 D CB 213 483 305 88 310 D CG 226 490 300 105 310 D OD1 233 483 293 105 310 D OD2 228 502 303 116 311 T N 193 496 283 88 311 T CA 190 506 272 87 311 T C 190 520 277 92 311 T O 200 527 276 93 311 T CB 177 502 265 92 311 T OG1 168 499 275 89 311 T CG2 179 490 255 90 312 A N 178 525 281 89 312 A CA 176 538 286 89 312 A C 177 537 301 93 312 A O 186 542 307 93 312 A CB 163 544 282 90 313 G N 168 530 307 88 313 G CA 167 527 321 87 313 G C 177 516 325 90 313 G O 189 518 325 90 314 G N 172 505 328 86 314 G CA 180 493 332 86 314 G C 171 484 340 88 314 G O 172 471 340 89 315 F N 161 490 347 81 315 F CA 151 482 355 79 315 F C 137 486 350 84 315 F O 129 477 346 82 315 F CB 153 483 370 80 315 F CG 155 470 377 81 315 F CD1 144 463 381 83 315 F CD2 167 465 378 83 315 F CE1 145 450 387 83 315 F CE2 169 452 384 85 315 F CZ 158 445 389 83 316 Q N 134 499 352 81 316 Q CA 121 504 348 81 316 Q C 118 501 333 83 316 Q O 107 499 329 82 316 Q CB 121 519 351 83 316 Q CG 108 526 346 110 316 Q CD 104 538 355 133 316 Q OE1 112 545 360 127 316 Q NE2 91 540 356 127 317 Q N 129 501 325 79 317 Q CA 127 499 311 78 317 Q C 125 484 307 82 317 Q O 115 481 300 81 317 Q CB 140 503 303 80 317 Q CG 138 504 288 95 317 Q CD 130 516 284 119 317 Q OE1 134 528 284 113 317 Q NE2 117 513 279 120 318 L N 133 475 313 77 318 L CA 131 461 311 75 318 L C 118 456 317 76 318 L O 112 447 311 75 318 L CB 143 453 317 75 318 L CG 157 454 311 80 318 L CD1 166 445 318 80 318 L CD2 156 452 296 82 319 L N 114 462 328 69 319 L CA 101 458 334 68 319 L C 89 460 326 72 319 L O 78 457 330 72 319 L CB 100 464 348 69 319 L CG 110 461 359 74 319 L CD1 113 474 368 74 319 L CD2 107 449 367 77 320 L N 91 466 314 68 320 L CA 79 469 306 68 320 L C 75 457 298 70 320 L O 63 456 294 71 320 L CB 82 481 296 69 320 L CG 87 494 304 74 320 L CD1 88 505 294 74 320 L CD2 78 497 315 77 321 E N 84 447 295 63 321 E CA 80 435 288 62 321 E C 75 425 299 65 321 E O 82 422 309 65 321 E CB 92 429 281 63 321 E CG 92 432 266 71 321 E CD 83 423 259 88 321 E OE1 81 425 247 76 321 E OE2 76 415 266 85 322 P N 63 420 297 58 322 P CA 57 411 307 57 322 P C 65 399 310 61 322 P O 64 394 321 59 322 P CB 44 408 300 59 322 P CG 40 420 291 63 322 P CD 53 426 288 58 323 M N 73 394 300 58 323 M CA 80 382 303 57 323 M C 93 385 311 57 323 M O 96 377 320 57 323 M CB 84 375 290 59 323 M CG 88 360 291 64 323 M SD 75 349 300 69 323 M CE 84 341 312 66 324 L N 99 396 310 50 324 L CA 110 400 318 49 324 L C 105 403 332 50 324 L O 110 397 342 49 324 L CB 118 411 312 49 324 L CG 119 409 297 54 324 L CD1 129 420 291 55 324 L CD2 124 395 293 56 325 K N 95 411 333 45 325 K CA 89 414 346 44 325 K C 85 401 354 45 325 K O 87 400 366 42 325 K CB 77 423 345 44 325 K CG 71 427 358 71 325 K CD 60 437 356 83 325 K CE 59 447 368 99 325 K NZ 46 445 376 111 326 F N 80 392 346 40 326 F CA 76 379 353 40 326 F C 88 372 359 42 326 F O 88 366 370 42 326 F CB 68 370 343 42 326 F CG 66 356 347 44 326 F CD1 55 352 353 48 326 F CD2 76 346 346 46 326 F CE1 53 339 359 50 326 F CE2 75 334 351 49 326 F CZ 63 330 358 47 327 H N 100 372 352 37 327 H CA 112 365 357 35 327 H C 118 372 369 42 327 H O 122 366 379 41 327 H CB 123 363 345 35 327 H CG 120 352 337 38 327 H ND1 124 339 340 39 327 H CD2 114 350 325 39 327 H CE1 120 330 331 39 327 H NE2 114 337 321 39 328 Y N 118 386 368 40 328 Y CA 123 393 380 42 328 Y C 114 391 392 42 328 Y O 120 390 403 42 328 Y CB 124 408 376 43 328 Y CG 137 411 369 47 328 Y CD1 138 413 355 50 328 Y CD2 149 411 376 48 328 Y CE1 150 415 349 52 328 Y CE2 161 413 369 50 328 Y CZ 162 415 356 58 328 Y OH 174 417 349 61 329 M N 101 391 390 42 329 M CA 92 389 401 42 329 M C 92 375 407 44 329 M O 92 373 419 47 329 M CB 77 392 397 46 329 M CG 76 406 392 53 329 M SD 58 411 391 62 329 M CE 50 397 400 58 330 L N 92 365 398 38 330 L CA 92 351 403 36 330 L C 105 348 410 41 330 L O 104 342 421 42 330 L CB 90 341 391 35 330 L CG 88 326 395 38 330 L CD1 79 325 407 37 330 L CD2 84 317 383 31 331 K N 116 354 405 39 331 K CA 129 352 412 36 331 K C 129 358 426 42 331 K O 137 354 435 41 331 K CB 141 357 403 35 331 K CG 154 351 408 34 331 K CD 157 337 402 39 331 K CE 170 331 408 26 331 K NZ 172 318 402 38 332 K N 122 369 427 41 332 K CA 121 377 439 41 332 K C 115 369 451 47 332 K O 119 372 463 51 332 K CB 111 389 437 44 332 K CG 114 401 445 51 332 K CD 103 412 442 66 332 K CE 105 424 451 82 332 K NZ 92 433 452 90 333 L N 105 360 448 39 333 L CA 99 352 458 35 333 L C 108 342 464 41 333 L O 104 336 474 42 333 L CB 86 345 452 34 333 L CG 76 355 445 37 333 L CD1 64 348 440 33 333 L CD2 72 365 456 33 334 Q N 119 339 458 40 334 Q CA 129 329 463 37 334 Q C 123 315 466 40 334 Q O 126 310 477 38 334 Q CB 137 334 475 40 334 Q CG 144 348 472 55 334 Q CD 150 354 484 72 334 Q OE1 162 351 487 65 334 Q NE2 143 362 492 66 335 L N 117 309 457 37 335 L CA 110 296 459 34 335 L C 120 285 460 41 335 L O 131 285 455 36 335 L CB 100 293 448 33 335 L CG 90 304 444 36 335 L CD1 81 299 434 33 335 L CD2 83 309 457 38 336 H N 115 274 466 42 336 H CA 122 262 468 44 336 H C 120 253 456 44 336 H O 111 257 447 41 336 H CB 118 255 481 48 336 H CG 120 264 494 53 336 H ND1 115 262 506 55 336 H CD2 128 275 495 56 336 H CE1 120 271 515 55 336 H NE2 128 279 508 56 337 E N 128 243 454 39 337 E CA 126 234 442 37 337 E C 112 228 442 39 337 E O 106 227 431 37 337 E CB 136 222 444 38 337 E CG 151 226 444 39 337 E CD 157 230 430 59 337 E OE1 149 232 420 38 337 E OE2 169 231 429 44 338 E N 107 225 454 35 338 E CA 94 218 456 34 338 E C 83 227 451 38 338 E O 73 222 445 37 338 E CB 92 215 471 35 338 E CG 100 203 475 38 338 E CD 115 206 479 54 338 E OE1 122 196 483 50 338 E OE2 119 218 480 45 339 E N 84 240 453 36 339 E CA 74 250 449 34 339 E C 74 253 435 34 339 E O 64 253 428 37 339 E CB 77 264 457 35 339 E CG 74 262 472 36 339 E CD 81 273 481 53 339 E OE1 91 280 476 32 339 E OE2 77 275 493 38 340 Y N 86 253 429 30 340 Y CA 87 254 414 31 340 Y C 81 241 407 35 340 Y O 73 242 397 35 340 Y CB 101 254 410 32 340 Y CG 107 268 409 32 340 Y CD1 117 272 418 33 340 Y CD2 103 278 400 31 340 Y CE1 123 285 417 33 340 Y CE2 109 291 399 29 340 Y CZ 119 294 408 34 340 Y OH 125 306 409 28 341 V N 83 230 413 31 341 V CA 78 218 407 31 341 V C 63 216 408 36 341 V O 57 211 398 37 341 V CB 86 205 411 36 341 V CG1 78 199 424 37 341 V CG2 87 196 400 36 342 L N 58 221 419 36 342 L CA 43 220 421 34 342 L C 36 231 412 38 342 L O 25 228 407 42 342 L CB 39 224 436 34 342 L CG 43 213 446 34 342 L CD1 44 218 460 34 342 L CD2 32 202 445 34 343 M N 43 242 409 31 343 M CA 38 252 400 29 343 M C 38 246 386 35 343 M O 29 250 379 36 343 M CB 48 264 400 31 343 M CG 45 275 409 35 343 M SD 57 288 407 37 343 M CE 49 299 395 33 344 Q N 48 238 383 32 344 Q CA 48 231 370 32 344 Q C 36 221 369 35 344 Q O 29 220 359 37 344 Q CB 62 223 369 34 344 Q CG 74 231 365 27 344 Q CD 87 223 363 42 344 Q OE1 97 228 366 30 344 Q NE2 86 210 360 26 345 A N 34 213 379 31 345 A CA 22 204 380 31 345 A C 9 212 378 38 345 A O 1 208 370 40 345 A CB 22 197 394 32 346 I N 7 223 386 34 346 I CA −5 231 385 34 346 I C −7 236 371 40 346 I O −19 236 366 43 346 I CB −5 242 395 35 346 I CG1 −8 237 409 32 346 I CG2 −16 253 391 34 346 I CD1 −2 246 421 33 347 S N 3 242 365 36 347 S CA 2 247 351 36 347 S C −1 235 341 41 347 S O −8 237 331 43 347 S CB 15 254 347 42 347 S OG 18 254 333 46 348 L N 5 224 342 36 348 L CA 4 213 333 35 348 L C −11 207 334 41 348 L O −17 205 324 41 348 L CB 14 201 337 33 348 L CG 13 189 328 34 348 L CD1 17 192 314 34 348 L CD2 22 177 335 32 349 F N −16 205 346 39 349 F CA −29 199 348 41 349 F C −40 211 349 46 349 F O −47 212 358 50 349 F CB −30 191 361 42 349 F CG −22 178 360 43 349 F CD1 −9 177 363 46 349 F CD2 −28 166 355 45 349 F CE1 −2 165 362 47 349 F CE2 −21 155 354 45 349 F CZ −8 154 357 44 350 S N −40 219 338 41 350 S N −40 219 338 43 350 S CA −50 230 337 42 350 S CA −50 230 338 45 350 S CB −44 241 328 41 350 S CB −44 242 332 46 350 S OG −35 249 335 36 350 S OG −50 246 320 54 350 S C −62 224 329 51 350 S C −62 225 330 52 350 S O −61 220 318 51 350 S O −61 224 317 52 351 P N −73 224 336 50 351 P CA −86 218 330 52 351 P C −91 226 318 58 351 P O −99 220 310 57 351 P CB −96 218 342 53 351 P CG −91 230 351 56 351 P CD −76 230 349 50 352 D N −87 238 316 57 352 D CA −93 247 306 58 352 D C −84 249 293 63 352 D O −85 259 287 66 352 D CB −97 260 311 61 352 D CG −87 267 321 74 352 D OD1 −76 262 322 72 352 D OD2 −90 277 327 80 353 R N −76 239 290 58 353 R CA −68 240 278 57 353 R C −77 237 266 60 353 R O −85 227 266 60 353 R CB −56 230 279 51 353 R CG −47 232 290 54 353 R CD −41 245 290 60 353 R NE −29 246 299 66 353 R CZ −23 257 302 68 353 R NH1 −26 269 296 49 353 R NH2 −12 256 310 54 354 P N −75 244 255 56 354 P CA −82 241 243 56 354 P C −81 227 239 65 354 P O −70 223 234 67 354 P CB −76 251 233 57 354 P CG −71 262 241 61 354 P CD −67 256 254 56 355 G N −91 219 240 62 355 G CA −91 205 235 61 355 G C −91 194 245 67 355 G O −88 182 242 67 356 V N −95 197 258 65 356 V CA −95 187 269 65 356 V C −109 181 271 70 356 V O −119 188 272 70 356 V CB −90 194 282 68 356 V CG1 −93 185 294 68 356 V CG2 −74 195 281 68 357 L N −109 168 271 66 357 L CA −122 161 273 65 357 L C −125 157 288 67 357 L O −136 159 293 68 357 L CB −123 148 264 65 357 L CG −124 151 249 70 357 L CD1 −129 139 242 71 357 L CD2 −133 163 246 69 358 Q N −115 152 295 60 358 Q CA −116 149 309 59 358 Q C −115 162 318 63 358 Q O −106 162 326 62 358 Q CB −105 139 312 60 358 Q CG −105 126 304 64 358 Q CD −116 116 310 94 358 Q OE1 −123 119 319 89 358 Q NE2 −117 105 303 95 359 H N −124 171 316 60 359 H N −123 171 316 59 359 H CA −124 184 323 61 359 H CA −123 184 324 59 359 H CB −136 192 318 62 359 H CB −135 193 320 61 359 H CG −137 206 323 66 359 H CG −136 206 328 64 359 H ND1 −143 209 335 68 359 H ND1 −142 217 323 66 359 H CE1 −142 222 337 68 359 H CE1 −140 227 332 65 359 H NE2 −135 228 327 68 359 H NE2 −134 222 343 65 359 H CD2 −132 218 318 68 359 H CD2 −131 209 340 66 359 H C −124 182 338 66 359 H C −123 181 338 65 359 H O −117 188 345 66 359 H O −115 186 346 66 360 R N −133 173 342 63 360 R CA −135 170 357 64 360 R C −123 163 363 66 360 R O −119 168 374 66 360 R CB −148 161 359 69 360 R CG −145 148 367 90 360 R CD −154 137 362 108 360 R NE −162 131 373 122 360 R CZ −167 118 373 137 360 R NH1 −164 110 362 122 360 R NH2 −174 114 383 128 361 V N −117 153 357 60 361 V CA −106 146 362 59 361 V C −94 155 364 59 361 V O −88 156 375 57 361 V CB −102 134 354 64 361 V CG1 −91 126 361 65 361 V CG2 −115 125 353 63 362 V N −90 163 354 53 362 V CA −79 172 353 52 362 V C −80 183 364 59 362 V O −71 187 371 57 362 V CB −77 178 339 55 362 V CG1 −67 189 340 55 362 V CG2 −73 168 329 54 363 D N −93 188 366 56 363 D CA −96 198 375 55 363 D C −94 193 390 58 363 D O −87 200 397 57 363 D CB −110 203 374 58 363 D CG −113 215 382 67 363 D OD1 −118 225 376 66 363 D OD2 −111 215 394 73 364 Q N −98 181 393 55 364 Q CA −96 176 406 56 364 Q C −81 174 408 58 364 Q O −76 175 420 59 364 Q CB −104 162 408 57 364 Q CG −118 162 403 75 364 Q CD −124 149 404 100 364 Q OE1 −118 138 406 97 364 Q NE2 −138 148 403 89 365 L N −74 169 398 52 365 L CA −60 168 398 52 365 L C −53 181 402 48 365 L O −44 182 411 47 365 L CB −54 162 385 52 365 L CG −58 147 384 56 365 L CD1 −56 142 369 57 365 L CD2 −49 138 392 54 366 Q N −57 191 395 42 366 Q CA −51 205 396 42 366 Q C −53 210 411 50 366 Q O −44 217 416 49 366 Q CB −56 215 386 43 366 Q CG −49 228 386 39 366 Q CD −56 239 378 50 366 Q OE1 −68 240 378 52 366 Q NE2 −48 247 370 35 367 E N −64 206 417 46 367 E CA −68 210 430 46 367 E C −59 203 440 48 367 E O −54 209 450 47 367 E CB −83 207 433 49 367 E CG −91 218 439 64 367 E CD −102 213 448 102 367 E OE1 −104 201 450 98 367 E OE2 −109 221 454 108 368 Q N −57 191 438 45 368 Q N −57 191 438 44 368 Q CA −48 183 446 45 368 Q CA −48 183 448 44 368 Q CB −46 169 440 46 368 Q CB −49 168 445 45 368 Q CG −57 158 444 64 368 Q CG −63 162 447 48 368 Q CD −53 144 440 80 368 Q CD −72 169 458 54 368 Q OE1 −59 138 431 73 368 Q OE1 −69 168 469 47 368 Q NE2 −43 139 446 75 368 Q NE2 −83 175 453 45 368 Q C −35 189 447 46 368 Q C −34 188 447 45 368 Q O −29 190 458 46 368 Q O −27 187 458 45 369 F N −29 194 436 40 369 F CA −16 199 435 38 369 F C −16 213 442 43 369 F O −7 216 449 46 369 F CB −11 200 421 37 369 F CG −7 187 415 37 369 F CD1 −14 183 404 40 369 F CD2 3 179 420 40 369 F CE1 −11 170 398 41 369 F CE2 7 167 414 42 369 F CZ −1 163 402 41 370 A N −26 221 439 43 370 A CA −27 234 445 42 370 A C −28 233 460 42 370 A O −22 240 468 42 370 A CB −39 242 439 43 371 I N −36 223 465 40 371 I CA −37 221 480 39 371 I C −24 216 486 42 371 I O −20 221 496 44 371 I CB −49 210 483 43 371 I CG1 −62 217 480 44 371 I CG2 −48 205 497 39 371 I CD1 −74 207 478 39 372 T N −17 207 479 38 372 T CA −3 203 483 36 372 T C 6 215 484 40 372 T O 14 215 494 39 372 T CB 3 193 473 42 372 T OG1 −6 182 472 39 372 T CG2 17 189 478 43 373 L N 6 224 475 37 373 L CA 14 236 474 37 373 L C 11 245 486 41 373 L O 20 250 493 41 373 L CB 13 243 461 36 373 L CG 20 257 460 41 373 L CD1 36 255 464 40 373 L CD2 19 263 446 37 374 K N −2 247 488 39 374 K CA −8 255 499 39 374 K C −3 250 512 45 374 K O 2 258 521 48 374 K CB −23 255 498 43 374 K CG −30 266 506 55 374 K CD −45 264 505 51 374 K CE −53 275 513 62 374 K NZ −61 285 504 69 375 S N −4 237 515 41 375 S CA 1 232 527 41 375 S C 16 231 529 45 375 S O 21 233 540 45 375 S CB −5 218 529 44 375 S OG −18 218 523 54 376 Y N 23 229 518 42 376 Y CA 37 229 518 42 376 Y C 42 243 524 45 376 Y O 51 243 532 46 376 Y CB 43 227 504 42 376 Y CG 58 228 504 44 376 Y CD1 64 240 503 45 376 Y CD2 66 217 506 43 376 Y CE1 78 241 502 47 376 Y CE2 79 218 506 43 376 Y CZ 85 230 505 50 376 Y OH 99 231 505 47 377 I N 36 253 519 40 377 I CA 39 267 523 39 377 I C 36 270 537 46 377 I O 43 276 545 47 377 I CB 32 277 513 42 377 I CG1 38 276 499 41 377 I CG2 32 292 519 42 377 I CD1 31 285 489 41 378 E N 24 266 542 46 378 E CA 19 267 556 47 378 E C 29 260 565 56 378 E O 32 265 576 57 378 E CB 6 260 558 48 378 E CG −7 268 553 57 378 E CD −19 258 554 81 378 E OE1 −18 248 561 75 378 E OE2 −30 261 547 67 379 C N 34 248 561 54 379 C CA 43 240 569 55 379 C C 57 245 569 59 379 C O 64 243 579 58 379 C CB 43 226 565 57 379 C SG 26 218 567 63 380 N N 62 249 558 57 380 N CA 76 251 556 56 380 N C 81 266 557 62 380 N O 93 269 557 63 380 N CB 82 245 544 49 380 N CG 83 229 545 64 380 N OD1 91 224 552 61 380 N ND2 73 223 540 46 381 R N 71 275 559 61 381 R CA 74 289 560 63 381 R C 61 295 567 73 381 R O 54 303 562 73 381 R CB 76 296 546 63 381 R CG 69 289 534 68 381 R CD 77 289 521 59 381 R NE 86 300 520 58 381 R CZ 94 303 510 57 381 R NH1 94 296 499 39 381 R NH2 101 314 511 45 382 P N 59 291 579 73 382 P CA 47 295 587 73 382 P C 48 310 591 76 382 P O 38 316 595 73 382 P CB 46 286 599 75 382 P CG 60 281 601 79 382 P CD 67 281 587 74 383 Q N 60 315 590 73 383 Q CA 62 329 594 73 383 Q C 52 338 587 78 383 Q O 52 339 575 79 383 Q CB 76 334 590 75 383 Q CG 88 326 596 90 383 Q CD 90 313 590 104 383 Q OE1 87 311 578 90 383 Q NE2 95 303 598 104 384 P N 43 344 595 74 384 P CA 33 353 589 72 384 P C 38 362 577 72 384 P O 30 367 570 73 384 P CB 30 362 601 73 384 P CG 31 353 613 78 384 P CD 39 341 609 74 385 A N 51 362 575 64 385 A CA 56 370 564 63 385 A C 52 364 550 63 385 A O 51 371 540 63 385 A CB 72 372 564 64 386 H N 50 350 550 57 386 H CA 47 342 538 56 386 H C 32 339 538 56 386 H O 28 330 530 56 386 H CB 55 330 538 57 386 H CG 70 333 537 61 386 H ND1 78 332 548 63 386 H CD2 78 337 527 63 386 H CE1 91 335 544 63 386 H NE2 91 338 532 64 387 R N 23 346 545 48 387 R CA 9 345 545 45 387 R C 1 344 532 44 387 R O −8 337 531 39 387 R CB 3 356 554 45 387 R CG −11 357 555 40 387 R CD −15 368 565 42 387 R NE −30 370 565 37 387 R CZ −36 380 569 51 387 R NH1 −30 390 576 33 387 R NH2 −49 380 568 30 388 F N 5 353 523 37 388 F CA −1 353 509 36 388 F C 7 347 498 38 388 F O 4 349 487 37 388 F CB −6 367 506 36 388 F CG −18 371 513 37 388 F CD1 −19 384 518 39 388 F CD2 −29 363 516 40 388 F CE1 −31 388 526 37 388 F CE2 −40 367 523 41 388 F CZ −41 380 527 35 389 L N 18 340 501 36 389 L CA 27 334 491 37 389 L C 20 325 481 40 389 L O 22 325 469 41 389 L CB 39 327 498 37 389 L CG 49 323 487 42 389 L CD1 55 334 478 39 389 L CD2 61 315 495 38 390 F N 11 316 486 36 390 F CA 3 308 477 34 390 F C −5 316 467 39 390 F O −4 313 455 40 390 F CB −6 298 486 34 390 F CG −15 290 477 36 390 F CD1 −11 280 470 38 390 F CD2 −29 294 477 37 390 F CE1 −20 272 462 38 390 F CE2 −38 286 469 39 390 F CZ −33 276 462 38 391 L N −12 326 472 38 391 L CA −20 334 463 36 391 L C −12 342 453 40 391 L O −16 343 441 42 391 L CB −29 343 471 36 391 L CG −40 336 479 38 391 L CD1 −46 346 490 39 391 L CD2 −51 331 471 38 392 K N 0 346 457 37 392 K CA 9 353 449 36 392 K C 13 344 437 41 392 K O 11 347 425 42 392 K CB 21 357 457 38 392 K CG 19 369 465 56 392 K CD 32 374 472 65 392 K CE 29 385 482 53 392 K NZ 42 388 489 73 393 I N 18 332 441 37 393 I CA 22 322 431 36 393 I C 10 319 421 38 393 I O 13 318 409 39 393 I CB 25 309 438 37 393 I CG1 38 311 447 33 393 I CG2 26 297 427 37 393 I CD1 43 298 454 32 394 M N −2 318 426 37 394 M CA −13 315 417 37 394 M C −16 327 408 43 394 M O −20 325 397 44 394 M CB −26 311 425 38 394 M CG −25 299 433 41 394 M SD −21 283 424 45 394 M CE −37 280 418 42 395 A N −13 339 413 40 395 A CA −14 351 405 40 395 A C −4 350 393 43 395 A O −7 354 382 42 395 A CB −13 363 413 40 396 M N 8 346 396 42 396 M CA 19 345 386 42 396 M C 15 335 376 43 396 M O 17 336 364 42 396 M CB 32 341 393 45 396 M CG 36 351 404 49 396 M SD 47 362 398 55 396 M CE 58 361 412 53 397 L N 9 324 380 39 397 L CA 5 313 371 40 397 L C −6 318 361 49 397 L O −6 313 349 47 397 L CB −1 301 379 38 397 L CG 10 293 386 41 397 L CD1 3 280 391 39 397 L CD2 22 289 376 39 398 T N −14 327 365 46 398 T CA −24 333 357 45 398 T C −18 343 347 50 398 T O −21 343 335 49 398 T CB −35 340 365 55 398 T OG1 −44 331 372 47 398 T CG2 −44 349 356 56 399 E N −9 352 351 48 399 E CA −3 361 343 48 399 E C 6 353 332 51 399 E O 5 356 320 54 399 E CB 6 371 351 50 399 E CG 18 378 343 64 399 E CD 13 390 335 80 399 E OE1 1 391 334 82 399 E OE2 22 397 331 82 400 L N 13 343 337 44 400 L CA 21 334 328 43 400 L C 12 328 317 47 400 L O 17 326 306 44 400 L CB 27 323 336 42 400 L CG 37 314 328 43 400 L CD1 47 321 321 41 400 L CD2 43 303 337 40 401 R N 0 326 320 44 401 R CA −9 320 311 46 401 R C −14 330 300 55 401 R O −17 326 289 55 401 R CB −21 313 317 48 401 R CG −31 308 308 59 401 R CD −41 300 316 74 401 R NE −51 294 307 83 401 R CZ −57 283 310 96 401 R NH1 −54 276 322 85 401 R NH2 −65 277 302 76 402 S N −13 343 304 51 402 S CA −16 353 294 50 402 S C −4 355 285 52 402 S O −5 357 274 51 402 S CB −20 367 301 57 402 S OG −12 377 296 72 403 I N 8 355 292 48 403 I CA 20 358 284 47 403 I C 22 347 273 48 403 I O 26 350 262 50 403 I CB 32 358 294 50 403 I CG1 31 370 304 50 403 I CG2 45 359 286 48 403 I CD1 42 370 314 46 404 N N 19 335 277 39 404 N CA 19 323 268 41 404 N C 11 326 255 47 404 N O 17 324 244 45 404 N CB 14 311 275 38 404 N CG 15 298 266 54 404 N OD1 21 299 256 49 404 N ND2 10 287 271 39 405 A N −1 330 257 45 405 A CA −10 333 246 45 405 A C −4 345 237 53 405 A O −4 344 225 55 405 A CB −24 336 250 46 406 Q N 1 355 244 48 406 Q CA 7 366 237 47 406 Q C 19 361 229 51 406 Q O 20 364 217 51 406 Q CB 12 377 247 50 406 Q CG 8 391 245 88 406 Q CD 20 400 240 116 406 Q OE1 25 408 248 116 406 Q NE2 24 399 228 101 407 H N 27 353 235 51 407 H CA 39 348 229 52 407 H C 37 338 217 54 407 H O 45 335 209 53 407 H CB 48 341 239 54 407 H CG 59 351 243 59 407 H ND1 73 348 241 62 407 H CD2 59 363 249 61 407 H CE1 80 358 246 62 407 H NE2 72 367 251 62 408 T N 25 331 217 52 408 T CA 22 322 207 52 408 T C 17 329 195 58 408 T O 17 324 184 60 408 T CB 11 312 211 58 408 T OG1 15 305 223 57 408 T CG2 8 302 201 53 409 Q N 11 341 197 57 409 Q CA 6 349 186 56 409 Q C 18 356 179 60 409 Q O 19 357 167 62 409 Q CB −3 360 191 58 409 Q CG −17 355 194 71 409 Q CD −27 367 198 113 409 Q OE1 −25 374 207 108 409 Q NE2 −37 369 189 116 410 R N 28 360 188 54 410 R CA 40 366 183 53 410 R C 47 356 174 54 410 R O 51 359 162 54 410 R CB 50 369 195 54 410 R CG 46 379 205 52 410 R CD 58 385 212 58 410 R NE 54 390 226 61 410 R CZ 61 400 232 81 410 R NH1 71 405 226 69 410 R NH2 57 404 244 80 411 L N 49 344 179 49 411 L CA 56 333 172 50 411 L C 49 330 158 56 411 L O 56 328 148 56 411 L CB 57 320 180 49 411 L CG 61 308 173 54 411 L CD1 76 306 172 54 411 L CD2 56 295 180 54 412 L N 36 330 158 53 412 L CA 29 326 146 53 412 L C 30 337 136 58 412 L O 31 334 124 59 412 L CB 14 324 149 53 412 L CG 12 310 155 59 412 L CD1 −3 305 156 59 412 L CD2 20 300 147 63 413 R N 31 350 140 55 413 R CA 33 361 131 54 413 R C 47 360 124 59 413 R O 47 361 112 62 413 R CB 32 374 139 52 413 R CG 17 378 143 60 413 R CD 15 393 145 53 413 R NE 20 397 158 57 413 R CZ 13 394 169 63 413 R NH1 2 387 169 53 413 R NH2 18 398 181 49 414 I N 57 358 132 56 414 I CA 71 357 127 56 414 I C 72 345 118 58 414 I O 77 345 107 59 414 I CB 81 355 138 59 414 I CG1 81 367 148 59 414 I CG2 95 353 133 57 414 I CD1 86 363 162 62 415 Q N 66 334 123 55 415 Q CA 66 321 115 56 415 Q C 61 323 101 63 415 Q O 66 318 91 63 415 Q CB 59 310 123 56 415 Q CG 57 297 115 45 415 Q CD 70 289 114 63 415 Q OE1 81 293 119 57 415 Q NE2 70 278 106 52 416 D N 50 331 100 59 416 D CA 42 334 88 59 416 D C 50 341 77 64 416 D O 48 338 65 65 416 D CB 30 342 91 61 416 D CG 21 343 79 77 416 D OD1 23 336 69 80 416 D OD2 12 352 80 79 417 I N 59 350 81 60 417 I CA 67 357 72 59 417 I C 82 352 71 63 417 I O 90 356 63 62 417 I CB 68 372 75 63 417 I CG1 78 375 86 64 417 I CG2 54 378 78 65 417 I CD1 77 389 92 61 418 H N 85 343 81 62 418 H CA 98 337 82 62 418 H C 99 324 89 66 418 H O 103 323 101 65 418 H CB 107 347 89 62 418 H CG 122 344 88 66 418 H ND1 129 338 98 67 418 H CD2 130 345 77 68 418 H CE1 142 336 93 67 418 H NE2 142 341 81 67 419 P N 95 313 82 62 419 P CA 95 300 88 61 419 P C 109 297 95 60 419 P O 119 298 90 59 419 P CB 93 290 76 63 419 P CG 96 299 64 68 419 P CD 92 312 68 63 420 F N 108 293 108 53 420 F CA 120 290 116 50 420 F C 117 279 126 52 420 F O 126 273 131 53 420 F CB 125 302 123 52 420 F CG 117 307 135 52 420 F CD1 121 304 148 55 420 F CD2 105 314 133 53 420 F CE1 113 307 159 55 420 F CE2 97 317 143 56 420 F CZ 101 314 156 54 421 A N 104 276 129 46 421 A CA 101 266 139 44 421 A C 105 252 135 48 421 A O 103 248 124 48 421 A CB 86 267 142 44 422 T N 110 244 145 44 422 T CA 113 230 143 44 422 T C 100 222 142 49 422 T O 89 227 145 51 422 T CB 120 225 156 44 422 T OG1 113 229 168 54 422 T CG2 134 228 156 32 423 P N 101 210 137 47 423 P CA 89 201 135 46 423 P C 82 200 148 49 423 P O 70 203 149 51 423 P CB 96 188 132 48 423 P CG 108 191 125 51 423 P CD 113 204 130 47 424 L N 89 198 159 42 424 L CA 83 197 173 40 424 L C 75 209 177 47 424 L O 65 208 183 49 424 L CB 93 193 183 38 424 L CG 87 191 197 41 424 L CD1 75 183 197 42 424 L CD2 96 186 208 33 425 M N 81 221 174 42 425 M CA 75 234 178 42 425 M C 62 236 169 49 425 M O 52 242 174 50 425 M CB 84 246 175 43 425 M CG 94 248 186 46 425 M SD 107 259 180 49 425 M CE 99 275 181 45 426 Q N 63 231 157 47 426 Q CA 52 232 147 46 426 Q C 40 225 153 52 426 Q O 28 230 154 53 426 Q CB 55 226 134 47 426 Q CG 63 236 125 64 426 Q CD 70 230 113 74 426 Q OE1 67 219 109 72 426 Q NE2 80 237 108 71 427 E N 42 213 159 47 427 E CA 31 206 165 47 427 E C 25 212 177 55 427 E O 13 212 179 55 427 E CB 36 192 168 49 427 E CG 38 183 156 50 427 E CD 38 169 160 65 427 E OE1 37 166 172 54 427 E OE2 41 160 151 59 428 L N 34 217 186 53 428 L CA 29 224 199 53 428 L C 22 237 196 63 428 L O 13 240 204 66 428 L CB 41 226 208 52 428 L CG 47 214 214 56 428 L CD1 61 216 220 55 428 L CD2 38 207 224 55 429 F N 25 244 186 63 429 F CA 18 257 183 65 429 F C 7 257 173 70 429 F O 1 268 171 71 429 F CB 29 268 181 68 429 F CG 38 270 192 70 429 F CD1 50 265 192 74 429 F CD2 32 274 204 72 429 F CE1 58 265 204 75 429 F CE2 39 274 216 75 429 F CZ 53 269 216 74 430 G N 5 246 166 67 430 G CA −5 245 156 66 430 G C −1 251 143 70 430 G O −10 257 135 73 431 I N 12 250 140 65 431 I CA 17 255 127 64 431 I C 18 244 117 71 431 I O 20 232 120 72 431 I CB 32 261 129 66 431 I CG1 32 271 141 65 431 I CG2 37 266 116 66 431 I CD1 46 276 145 53 444 S N −68 116 150 76 444 S CA −68 129 143 76 444 S C −60 139 150 79 444 S O −52 146 144 80 444 S CB −83 134 142 80 444 S OG −83 147 137 85 445 L N −62 140 163 74 445 L CA −54 149 172 73 445 L C −40 143 172 76 445 L O −30 151 173 76 445 L CB −60 150 186 73 445 L CG −56 161 195 76 445 L CD1 −55 174 187 76 445 L CD2 −66 162 206 77 446 T N −39 130 171 72 446 T CA −27 123 171 71 446 T C −20 122 157 74 446 T O −8 121 157 73 446 T CB −29 108 176 75 446 T OG1 −36 101 167 80 446 T CG2 −37 108 189 65 447 E N −28 123 147 69 447 E CA −23 123 133 68 447 E C −18 136 130 71 447 E O −10 138 121 72 447 E CB −34 118 123 70 447 E CG −29 120 108 85 447 E CD −32 108 100 114 447 E OE1 −41 99 104 120 447 E OE2 −26 107 89 115 448 R N −24 146 137 66 448 R CA −19 160 135 67 448 R C −8 163 144 69 448 R O −2 174 144 69 448 R CB −31 170 138 69 448 R CG −40 174 127 75 448 R CD −48 186 130 88 448 R NE −57 184 141 97 448 R CZ −59 192 152 112 448 R NH1 −51 202 153 112 448 R NH2 −68 189 161 82 449 H N −4 154 153 64 449 H CA 6 155 163 63 449 H C 14 142 164 63 449 H O 15 137 175 62 449 H CB −1 158 176 64 449 H CG −8 172 177 69 449 H ND1 −1 183 179 71 449 H CD2 −21 175 175 70 449 H CE1 −9 193 178 70 449 H NE2 −21 189 176 70 450 K N 20 138 153 59 450 K CA 28 125 153 58 450 K C 41 125 161 58 450 K O 43 115 168 58 450 K CB 30 120 139 60 450 K CG 18 112 133 71 450 K CD 20 110 118 84 450 K CE 8 117 110 91 450 K NZ 12 120 96 95 451 I N 49 135 161 51 451 I CA 61 136 169 50 451 I C 57 135 184 54 451 I O 63 126 191 50 451 I CB 69 148 166 52 451 I CG1 72 150 151 51 451 I CG2 82 148 174 52 451 I CD1 82 161 147 43 452 L N 48 144 188 52 452 L CA 44 144 202 51 452 L C 39 130 206 58 452 L O 43 126 217 57 452 L CB 33 154 204 50 452 L CG 35 167 212 53 452 L CD1 22 174 215 53 452 L CD2 43 164 224 52 453 H N 31 124 198 59 453 H CA 26 110 201 61 453 H C 38 100 203 64 453 H O 38 93 212 61 453 H CB 17 105 190 63 453 H CG 9 94 194 68 453 H ND1 14 81 197 72 453 H CD2 −5 93 196 71 453 H CE1 4 73 201 71 453 H NE2 −7 80 200 71 454 R N 47 100 193 59 454 R CA 58 91 193 58 454 R C 66 93 207 62 454 R O 68 84 214 64 454 R CB 68 94 182 54 454 R CG 82 88 183 62 454 R CD 92 94 173 65 454 R NE 105 88 174 86 454 R CZ 113 85 164 100 454 R NH1 110 89 152 87 454 R NH2 124 79 166 89 455 L N 69 106 210 57 455 L CA 76 110 222 55 455 L C 69 105 235 60 455 L O 75 102 245 58 455 L CB 79 125 222 53 455 L CG 90 130 213 56 455 L CD1 90 145 216 55 455 L CD2 103 124 216 55 456 L N 56 106 234 59 456 L CA 48 102 246 60 456 L C 47 87 248 68 456 L O 45 82 259 68 456 L CB 34 108 245 60 456 L CG 32 123 249 63 456 L CD1 19 128 245 62 456 L CD2 34 124 265 64 457 Q N 49 80 237 68 457 Q CA 48 65 237 70 457 Q CB 41 60 224 71 457 Q C 61 58 240 79 457 Q O 65 49 232 81 458 E N 68 62 250 77 458 E CA 81 56 254 77 458 E C 85 62 267 83 458 E O 96 57 273 84 458 E CB 91 60 243 78 458 E CG 89 74 238 91 458 E CD 101 79 230 107 458 E OE1 103 75 218 89 458 E OE2 108 88 235 99

TABLE 5b Crystal coordinates for crystalline complex of PXR-LBD-L10-SRC and SR12813 (crystal 3). The following table contains one line for each protein atom in the second of the two observed PXR-LBD-L10-SRC monomers complexed with SR12813 in the orthorhombic asymmetric unit. The columns are: 1) residue number, 2) 1-letter amino acid code, 3) atom name, 4) x-coordinate multiplied by 10, 5) y-coordinate multiplied by 10, 6) z-coordinate multiplied by 10, and 7) B-factor 142 G N 620 691 −58 73 142 G CA 615 683 −70 72 142 G C 622 669 −71 74 142 G O 634 668 −68 73 143 L N 615 659 −76 67 143 L CA 622 646 −79 65 143 L C 623 645 −94 67 143 L O 617 652 −102 67 143 L CB 613 635 −74 64 143 L CG 609 634 −59 66 143 L CD1 595 627 −58 65 143 L CD2 618 625 −51 67 144 T N 632 636 −98 63 144 T CA 635 635 −112 63 144 T C 623 628 −119 70 144 T O 614 623 −112 71 144 T CB 647 627 −115 69 144 T OG1 645 613 −111 72 144 T CG2 659 632 −107 68 145 E N 624 627 −132 67 145 E CA 614 620 −140 67 145 E C 613 606 −135 71 145 E O 603 600 −132 71 145 E CB 617 622 −155 69 145 E CG 605 618 −164 87 145 E CD 593 627 −162 110 145 E OE1 595 639 −167 97 145 E OE2 583 623 −156 105 146 E N 625 600 −135 66 146 E CA 627 586 −132 66 146 E C 622 582 −118 67 146 E O 617 571 −116 64 146 E CB 642 582 −134 68 146 E CG 646 568 −130 87 146 E CD 661 566 −128 120 146 E OE1 665 570 −117 129 146 E OE2 668 561 −137 109 147 Q N 623 592 −109 61 147 Q CA 619 589 −95 60 147 Q C 604 590 −93 64 147 Q O 598 581 −86 62 147 Q CB 626 598 −85 61 147 Q CG 640 593 −81 64 147 Q CD 649 604 −77 69 147 Q OE1 645 615 −75 52 147 Q NE2 662 601 −75 67 148 R N 598 599 −99 61 148 R CA 583 602 −99 59 148 R C 575 590 −105 63 148 R O 565 586 −100 63 148 R CB 579 614 −107 58 148 R CG 582 627 −100 68 148 R CD 581 638 −110 68 148 R NE 567 643 −109 81 148 R CZ 561 650 −119 82 148 R NH1 568 652 −130 65 148 R NH2 549 655 −118 49 149 M N 581 584 −115 60 149 M CA 574 573 −122 61 149 M C 576 560 −114 61 149 M O 568 551 −114 59 149 M CB 579 572 −136 65 149 M CG 589 562 −139 72 149 M SD 588 554 −155 80 149 M CE 590 570 −167 76 150 M N 588 559 −107 55 150 M CA 591 548 −99 53 150 M C 581 547 −87 52 150 M O 576 536 −84 49 150 M CB 605 549 −94 55 150 M CG 609 539 −82 59 150 M SD 626 542 −75 64 150 M CE 636 534 −87 60 151 I N 578 558 −81 47 151 I CA 569 559 −69 46 151 I C 554 557 −74 52 151 I O 546 550 −67 48 151 I CB 570 572 −63 48 151 I CG1 583 574 −56 47 151 I CG2 558 574 −53 50 151 I CD1 585 587 −50 43 152 R N 552 562 −86 50 152 R CA 538 560 −92 50 152 R C 536 545 −95 52 152 R O 525 540 −91 52 152 R CB 538 567 −106 52 152 R CG 528 579 −105 68 152 R CD 531 590 −116 73 152 R NE 538 585 −127 76 152 R CZ 547 592 −135 93 152 R NH1 550 604 −132 83 152 R NH2 553 586 −145 70 153 E N 545 538 −101 47 153 E CA 544 524 −103 47 153 E C 542 517 −90 51 153 E O 534 507 −89 53 153 E CB 557 518 −110 48 153 E CG 555 506 −118 63 153 E CD 567 497 −119 90 153 E OE1 578 501 −116 96 153 E OE2 565 485 −124 66 154 L N 550 520 −80 45 154 L CA 550 514 −67 41 154 L C 537 515 −60 41 154 L O 531 505 −55 38 154 L CB 561 520 −58 40 154 L CG 574 511 −54 44 154 L CD1 576 500 −64 42 154 L CD2 586 520 −51 42 155 M N 531 527 −61 36 155 M CA 518 531 −55 35 155 M C 506 524 −62 44 155 M O 497 519 −56 47 155 M CB 517 546 −55 37 155 M CG 525 554 −45 41 155 M SD 521 549 −28 46 155 M CE 511 563 −24 42 156 D N 507 524 −75 42 156 D CA 497 517 −83 42 156 D C 497 502 −80 46 156 D O 486 496 −79 49 156 D CB 500 519 −98 45 156 D CG 491 511 −107 54 156 D OD1 495 502 −114 60 156 D OD2 479 515 −108 48 157 A N 508 496 −78 42 157 A CA 510 482 −75 40 157 A C 504 478 −61 43 157 A O 500 467 −59 43 157 A CB 525 478 −75 40 158 Q N 506 488 −52 38 158 Q CA 501 486 −38 35 158 Q C 486 487 −38 38 158 Q O 479 478 −32 38 158 Q CB 507 498 −29 34 158 Q CG 503 497 −14 33 158 Q CD 512 489 −6 43 158 Q OE1 516 478 −10 37 158 Q NE2 516 495 6 28 159 M N 481 497 −44 36 159 M CA 466 498 −46 36 159 M C 460 485 −52 41 159 M O 450 480 −47 42 159 M CB 463 511 −54 38 159 M CG 448 513 −57 43 159 M SD 442 504 −73 47 159 M CE 452 514 −85 41 160 K N 465 481 −62 40 160 K CA 460 469 −69 40 160 K C 461 456 −61 42 160 K O 453 447 −64 44 160 K CB 467 467 −83 40 160 K CG 465 479 −92 47 160 K CD 472 476 −105 60 160 K CE 466 485 −116 59 160 K NZ 475 487 −128 71 161 T N 471 455 −53 37 161 T CA 474 442 −46 36 161 T C 472 442 −31 41 161 T O 475 432 −24 40 161 T CB 488 437 −50 38 161 T OG1 498 446 −45 46 161 T CG2 489 437 −65 43 162 F N 468 453 −25 39 162 F CA 466 454 −10 36 162 F C 452 457 −8 42 162 F O 447 467 −11 43 162 F CB 474 465 −4 35 162 F CG 474 465 11 35 162 F CD1 482 475 18 36 162 F CD2 468 455 19 35 162 F CE1 482 475 32 37 162 F CE2 469 455 33 36 162 F CZ 475 465 39 36 163 D N 444 447 −3 42 163 D CA 430 449 −1 44 163 D C 428 453 14 48 163 D O 427 444 23 46 163 D CB 421 438 −4 48 163 D CG 407 441 −1 68 163 D OD1 402 452 −4 63 163 D OD2 400 431 5 73 164 T N 430 465 16 45 164 T CA 429 471 30 46 164 T C 417 468 38 53 164 T O 417 469 50 57 164 T CB 433 485 30 48 164 T OG1 423 493 22 46 164 T CG2 447 487 24 42 165 T N 406 465 31 49 165 T CA 393 462 37 49 165 T C 391 447 40 52 165 T O 381 443 46 54 165 T CB 381 467 30 54 165 T OG1 378 460 18 54 165 T CG2 383 482 26 50 166 F N 401 439 36 47 166 F CA 400 424 38 46 166 F C 387 418 34 56 166 F O 382 408 39 56 166 F CB 404 420 52 46 166 F CG 418 424 56 45 166 F CD1 428 414 57 46 166 F CD2 422 437 58 44 166 F CE1 440 417 61 46 166 F CE2 435 440 61 45 166 F CZ 444 430 63 43 167 S N 381 423 23 55 167 S CA 369 418 17 57 167 S C 369 404 11 62 167 S O 360 396 12 64 167 S CB 363 427 7 62 167 S OG 372 438 5 71 168 H N 380 401 4 60 168 H CA 382 388 −2 59 168 H C 389 378 7 59 168 H O 393 367 2 60 168 H CB 389 389 −16 61 168 H CG 383 399 −25 66 168 H ND1 369 401 −25 68 168 H CD2 388 408 −33 68 168 H CE1 366 411 −33 67 168 H NE2 378 416 −39 67 169 F N 390 381 20 53 169 F CA 396 371 30 52 169 F C 384 363 35 59 169 F O 377 367 45 56 169 F CB 403 378 41 52 169 F CG 410 369 51 51 169 F CD1 415 357 47 53 169 F CD2 410 372 65 51 169 F CE1 421 348 56 51 169 F CE2 415 363 74 53 169 F CZ 421 351 69 50 170 K N 382 351 30 60 170 K CA 371 343 34 60 170 K C 375 328 37 66 170 K O 387 324 36 67 170 K CB 361 342 22 63 170 K CG 354 356 20 79 170 K CD 350 357 5 83 170 K CE 343 370 2 95 170 K NZ 333 369 −8 104 171 N N 366 321 41 63 171 N CA 368 307 44 63 171 N C 380 304 53 64 171 N O 386 293 51 66 171 N CB 368 298 31 61 171 N CG 358 302 21 81 171 N OD1 346 301 24 80 171 N ND2 362 306 9 74 172 F N 383 313 62 55 172 F CA 394 310 71 53 172 F C 389 302 83 58 172 F O 377 300 85 61 172 F CB 400 323 76 54 172 F CG 390 333 80 53 172 F CD1 385 334 93 52 172 F CD2 385 343 71 55 172 F CE1 376 343 97 54 172 F CE2 376 352 75 57 172 F CZ 371 352 88 56 173 R N 399 297 91 53 173 R CA 396 289 103 54 173 R C 395 298 115 60 173 R O 401 308 116 60 173 R CB 407 279 106 53 173 R CG 408 267 97 61 173 R CD 420 259 100 56 173 R NE 432 265 94 64 173 R CZ 444 259 93 81 173 R NH1 445 247 97 71 173 R NH2 454 265 88 69 174 L N 387 293 125 58 174 L CA 385 300 137 56 174 L C 386 290 149 62 174 L O 384 278 147 62 174 L CB 372 308 138 56 174 L CG 370 319 128 59 174 L CD1 356 322 124 56 174 L CD2 377 332 134 57 175 P N 390 295 161 59 175 P CA 392 286 172 59 175 P C 378 280 176 67 175 P O 368 287 178 69 175 P CB 396 296 183 59 175 P CG 396 309 178 63 175 P CD 396 308 163 58 176 G N 378 267 176 65 176 G CA 365 259 179 64 176 G C 356 265 189 68 176 G O 361 272 199 64 177 V N 343 262 188 67 177 V CA 333 268 197 67 177 V C 331 260 210 70 177 V O 331 265 221 69 177 V CB 319 269 190 71 177 V CG1 315 255 185 72 177 V CG2 309 275 199 71 193 R N 625 155 299 88 193 R CA 636 164 303 88 193 R CB 646 156 312 88 193 R C 643 171 292 92 193 R O 645 183 292 92 194 E N 646 164 281 89 194 E CA 652 169 269 88 194 E CB 660 158 262 89 194 E C 642 175 260 93 194 E O 642 188 258 93 195 E N 633 167 254 89 195 E CA 623 172 245 88 195 E CB 618 160 236 90 195 E C 611 179 252 93 195 E O 601 181 247 94 196 A N 613 182 265 89 196 A CA 603 188 273 89 196 A C 606 202 278 93 196 A O 597 209 283 95 196 A CB 600 179 286 90 197 A N 619 206 276 88 197 A CA 623 220 279 87 197 A C 621 229 267 89 197 A O 624 241 267 89 197 A CB 638 220 284 88 198 K N 616 223 256 83 198 K CA 613 230 244 82 198 K C 600 237 245 84 198 K O 597 246 237 84 198 K CB 614 220 232 85 198 K CG 627 212 231 100 198 K CD 626 202 219 109 198 K CE 640 197 215 120 198 K NZ 642 196 200 122 199 W N 591 231 254 79 199 W CA 578 237 256 77 199 W C 579 250 264 84 199 W O 571 259 262 85 199 W CB 569 226 263 75 199 W CG 564 215 255 74 199 W CD1 572 205 248 77 199 W CD2 550 212 252 74 199 W NE1 563 197 241 76 199 W CE2 550 201 243 77 199 W CE3 538 218 255 75 199 W CZ2 538 196 238 77 199 W CZ3 527 213 249 76 199 W CH2 527 202 241 77 200 S N 590 251 271 82 200 S CA 593 262 279 82 200 S C 596 275 271 86 200 S O 595 286 276 86 200 S CB 604 259 289 86 200 S OG 601 265 302 101 201 Q N 601 272 259 81 201 Q CA 604 283 250 80 201 Q C 593 286 240 83 201 Q O 590 298 237 84 201 Q CB 617 281 242 82 201 Q CG 621 293 233 105 201 Q CD 620 306 239 128 201 Q OE1 625 309 250 125 201 Q NE2 614 316 232 119 202 V N 586 276 236 77 202 V CA 574 277 227 76 202 V C 563 286 234 81 202 V O 556 293 227 80 202 V CB 569 264 222 78 202 V CG1 558 266 211 78 202 V CG2 580 255 217 78 203 R N 562 284 247 79 203 R CA 552 292 255 78 203 R C 557 306 256 83 203 R O 548 315 256 84 203 R CB 551 286 269 78 203 R CG 545 272 270 88 203 R CD 543 267 284 101 203 R NE 544 252 284 112 203 R CZ 550 245 294 120 203 R NH1 556 252 304 100 203 R NH2 550 232 293 100 204 K N 570 308 255 80 204 K CA 576 322 256 80 204 K CB 591 321 259 82 204 K C 573 329 243 85 204 K O 573 341 242 84 205 D N 571 321 232 82 205 D CA 568 327 219 81 205 D C 554 332 218 86 205 D O 552 343 211 88 205 D CB 570 316 208 82 205 D CG 585 310 209 88 205 D OD1 593 317 215 87 205 D OD2 587 299 203 91 206 L N 544 326 224 82 206 L CA 530 330 223 81 206 L C 526 341 233 86 206 L O 519 350 230 86 206 L CB 521 318 223 81 206 L CG 527 305 216 86 206 L CD1 526 293 225 87 206 L CD2 520 303 203 87 207 C N 530 339 246 83 207 C CA 525 348 257 84 207 C C 526 363 255 86 207 C O 516 370 260 86 207 C CB 530 343 271 85 207 C SG 548 339 272 90 208 S N 536 368 249 82 208 S CA 538 383 247 81 208 S C 530 387 235 82 208 S O 528 399 233 81 208 S CB 552 386 247 85 208 S OG 560 380 257 92 209 L N 526 377 226 76 209 L CA 520 380 214 75 209 L C 505 376 214 80 209 L O 499 371 204 80 209 L CB 527 371 203 75 209 L CG 542 374 201 78 209 L CD1 548 363 191 77 209 L CD2 544 388 195 79 210 K N 499 378 226 77 210 K CA 485 374 229 75 210 K C 474 384 225 74 210 K O 473 395 231 73 210 K CB 483 370 244 78 210 K CG 473 359 246 100 210 K CD 480 348 254 111 210 K CE 469 341 264 115 210 K NZ 462 351 272 120 211 V N 465 380 216 67 211 V CA 454 388 211 63 211 V C 440 383 213 61 211 V O 438 370 211 60 211 V CB 456 392 196 66 211 V CG1 468 401 195 66 211 V CG2 458 380 188 66 212 S N 430 391 214 52 212 S CA 416 387 213 51 212 S C 412 391 198 54 212 S O 419 399 191 55 212 S CB 407 395 222 51 212 S OG 410 409 222 56 213 L N 401 385 193 48 213 L CA 397 387 180 47 213 L C 382 391 179 52 213 L O 374 386 187 53 213 L CB 400 374 172 47 213 L CG 396 372 158 53 213 L CD1 402 360 152 52 213 L CD2 381 371 157 56 214 Q N 379 400 170 48 214 Q CA 366 405 168 46 214 Q C 361 404 154 56 214 Q O 369 406 145 57 214 Q CB 364 419 173 47 214 Q CG 351 425 170 56 214 Q CD 349 438 177 71 214 Q OE1 351 439 189 71 214 Q NE2 344 449 170 68 215 L N 349 399 151 56 215 L CA 344 398 138 57 215 L C 330 405 137 61 215 L O 321 402 144 61 215 L CB 342 383 134 57 215 L CG 354 375 132 63 215 L CD1 351 361 136 63 215 L CD2 359 376 118 65 216 R N 329 415 128 59 216 R CA 317 422 126 59 216 R C 310 417 114 67 216 R O 316 414 104 68 216 R CB 319 437 125 57 216 R CG 328 442 137 57 216 R CD 332 457 135 76 216 R NE 344 458 127 86 216 R CZ 356 454 132 94 216 R NH1 357 448 144 71 216 R NH2 367 456 125 78 217 G N 297 414 115 67 217 G CA 289 409 104 66 217 G C 284 421 97 72 217 G O 283 432 102 71 218 E N 281 419 84 71 218 E CA 276 430 75 72 218 E C 264 436 82 76 218 E O 261 448 80 78 218 E CB 273 425 61 75 218 E CG 260 430 56 96 218 E CD 261 442 47 125 218 E OE1 268 451 50 120 218 E OE2 254 442 36 119 219 D N 257 427 89 72 219 D CA 244 431 95 70 219 D C 245 440 107 70 219 D O 234 445 112 70 219 D CB 236 418 99 72 219 D CG 243 410 109 80 219 D OD1 251 416 118 77 219 D OD2 240 398 110 84 220 G N 257 442 113 65 220 G CA 258 450 125 65 220 G C 262 442 138 68 220 G O 268 448 147 69 221 S N 260 429 137 63 221 S CA 263 420 149 62 221 S C 279 419 151 64 221 S O 287 423 142 64 221 S CB 257 407 147 63 221 S OG 261 400 135 68 222 V N 283 414 162 58 222 V CA 297 412 166 57 222 V C 300 400 174 61 222 V O 294 397 184 59 222 V CB 302 424 173 60 222 V CG1 318 423 174 59 222 V CG2 298 437 166 59 223 W N 309 392 169 57 223 W CA 314 380 175 56 223 W C 328 383 181 58 223 W O 336 389 174 58 223 W CB 316 368 165 55 223 W CG 304 359 164 56 223 W CD1 297 358 153 59 223 W CD2 300 350 173 56 223 W NE1 288 348 154 58 223 W CE2 289 343 167 60 223 W CE3 303 347 187 56 223 W CZ2 282 333 174 59 223 W CZ3 296 337 193 58 223 W CH2 285 330 187 58 224 N N 330 381 194 53 224 N CA 343 384 200 52 224 N C 349 371 206 53 224 N O 341 363 212 53 224 N CB 341 394 211 49 224 N CG 353 401 215 84 224 N OD1 359 398 225 78 224 N ND2 359 410 206 72 225 Y N 362 369 204 48 225 Y CA 369 358 210 47 225 Y C 380 362 219 56 225 Y O 390 368 214 56 225 Y CB 375 349 199 47 225 Y CG 383 337 204 48 225 Y CD1 377 325 208 50 225 Y CD2 397 338 205 49 225 Y CE1 384 315 213 48 225 Y CE2 404 327 211 51 225 Y CZ 398 315 214 57 225 Y OH 405 304 219 61 226 K N 379 359 232 53 226 K CA 389 361 241 53 226 K C 397 348 243 59 226 K O 391 338 244 57 226 K CB 384 365 255 57 226 K CG 394 364 266 79 226 K CD 391 375 277 91 226 K CE 404 382 281 106 226 K NZ 402 392 292 111 227 P N 410 349 241 59 227 P CA 418 336 242 59 227 P C 418 330 256 65 227 P O 413 337 266 64 227 P CB 432 341 238 61 227 P CG 433 355 243 66 227 P CD 419 361 243 61 228 P N 422 318 257 63 228 P CA 424 311 270 64 228 P C 437 315 276 73 228 P O 447 315 269 74 228 P CB 423 296 267 65 228 P CG 426 295 252 68 228 P CD 420 308 246 64 229 A N 437 318 289 71 229 A CA 450 321 297 72 229 A C 459 308 297 77 229 A O 454 297 296 77 229 A CB 447 326 311 72 230 D N 472 311 298 75 230 D CA 482 299 298 76 230 D C 480 290 310 82 230 D O 484 293 321 82 230 D CB 496 304 296 78 230 D CG 506 292 294 93 230 D OD1 518 295 291 95 230 D OD2 502 280 295 97 231 S N 474 278 308 79 231 S CA 472 268 318 80 231 S C 473 254 313 86 231 S O 463 248 309 86 231 S CB 458 271 325 84 231 S OG 449 260 322 94 232 G N 485 248 315 82 232 G CA 488 235 309 81 232 G C 494 237 296 86 232 G O 504 245 294 87 233 G N 489 231 285 82 233 G CA 494 233 272 82 233 G C 485 227 261 87 233 G O 477 218 263 87 234 K N 485 233 249 83 234 K CA 478 229 237 82 234 K C 466 239 233 86 234 K O 463 241 221 87 234 K CB 473 215 237 85 234 K CG 466 210 224 108 234 K CD 472 197 219 120 234 K CE 487 198 217 133 234 K NZ 494 186 221 143 235 E N 460 245 243 82 235 E CA 450 255 241 81 235 E C 456 268 236 84 235 E O 450 275 228 85 235 E CB 443 258 254 82 235 E CG 451 264 265 93 235 E CD 458 254 274 112 235 E OE1 467 257 281 95 235 E OE2 453 242 273 100 236 I N 469 270 239 78 236 I CA 477 281 234 77 236 I C 480 282 219 78 236 I O 486 291 215 77 236 I CB 490 282 242 80 236 I CG1 500 271 238 80 236 I CG2 487 282 257 81 236 I CD1 514 273 244 84 237 F N 475 271 212 72 237 F CA 477 271 198 71 237 F C 464 272 191 72 237 F O 463 270 179 71 237 F CB 483 257 194 72 237 F CG 496 253 200 74 237 F CD1 496 242 209 78 237 F CD2 507 260 198 76 237 F CE1 508 238 215 79 237 F CE2 519 257 204 79 237 F CZ 519 246 213 78 238 S N 454 276 199 67 238 S CA 440 278 194 66 238 S C 438 288 182 66 238 S O 430 287 174 65 238 S CB 431 281 205 67 238 S OG 435 294 211 67 239 L N 446 299 183 62 239 L CA 445 310 173 60 239 L C 455 308 161 63 239 L O 456 317 153 60 239 L CB 448 323 180 60 239 L CG 435 331 184 65 239 L CD1 439 344 193 64 239 L CD2 426 335 172 65 240 L N 463 297 161 58 240 L CA 473 295 151 58 240 L C 468 292 137 63 240 L O 473 297 127 65 240 L CB 483 284 156 59 240 L CG 495 290 165 63 240 L CD1 506 280 165 63 240 L CD2 500 303 160 63 241 P N 459 282 136 58 241 P CA 453 279 123 57 241 P C 448 292 116 59 241 P O 451 294 104 58 241 P CB 442 269 126 58 241 P CG 445 263 138 63 241 P CD 452 274 146 59 242 H N 442 300 124 53 242 H CA 437 313 119 54 242 H C 448 323 115 54 242 H O 447 329 105 52 242 H CB 426 318 129 56 242 H CG 424 333 128 61 242 H ND1 429 341 117 65 242 H CD2 418 342 136 65 242 H CE1 427 354 119 64 242 H NE2 420 355 130 64 243 M N 458 325 124 51 243 M CA 469 334 121 51 243 M C 475 329 109 54 243 M O 481 337 101 53 243 M CB 479 333 133 55 243 M CG 476 341 145 60 243 M SD 465 354 143 67 243 M CE 465 362 161 64 244 A N 476 316 107 48 244 A CA 482 310 95 47 244 A C 473 314 82 50 244 A O 479 318 72 51 244 A CB 483 295 96 46 245 D N 460 312 83 44 245 D CA 452 316 72 45 245 D C 453 330 67 50 245 D O 452 334 56 51 245 D CB 437 312 74 48 245 D CG 435 297 76 57 245 D OD1 444 289 71 58 245 D OD2 426 294 83 68 246 M N 455 339 77 42 246 M CA 456 354 75 42 246 M C 469 357 69 45 246 M O 470 366 60 45 246 M CB 454 361 88 43 246 M CG 457 377 87 47 246 M SD 445 386 75 50 246 M CE 434 395 86 45 247 S N 479 351 74 42 247 S CA 493 353 70 43 247 S C 494 349 56 47 247 S O 501 356 47 45 247 S CB 502 345 78 47 247 S OG 508 353 88 57 248 T N 488 338 52 43 248 T CA 488 332 39 42 248 T C 481 342 29 45 248 T O 486 345 19 46 248 T CB 482 318 38 47 248 T OG1 490 309 47 51 248 T CG2 483 312 24 47 249 Y N 469 347 34 40 249 Y CA 462 356 26 40 249 Y C 471 369 23 44 249 Y O 472 373 11 44 249 Y CB 449 361 33 41 249 Y CG 441 371 25 44 249 Y CD1 434 368 14 46 249 Y CD2 441 385 30 45 249 Y CE1 427 378 7 47 249 Y CE2 434 394 23 46 249 Y CZ 427 391 12 55 249 Y OH 419 401 5 61 250 M N 478 374 33 40 250 M CA 487 385 31 39 250 M C 499 382 22 42 250 M O 503 391 14 39 250 M CB 492 390 45 42 250 M CG 482 395 54 46 250 M SD 476 412 50 51 250 M CE 492 422 51 46 251 F N 505 371 24 39 251 F CA 516 367 15 41 251 F C 512 366 1 43 251 F O 520 369 −8 45 251 F CB 523 354 19 44 251 F CG 529 354 33 46 251 F CD1 528 343 41 48 251 F CD2 535 365 38 47 251 F CE1 534 343 54 50 251 F CE2 542 365 50 50 251 F CZ 541 354 58 49 252 K N 500 363 −2 39 252 K CA 496 361 −16 38 252 K C 494 375 −22 43 252 K O 496 377 −34 43 252 K CB 483 353 −17 40 252 K CG 484 339 −13 53 252 K CD 470 332 −12 67 252 K CE 470 320 −22 92 252 K NZ 467 307 −14 105 253 G N 490 385 −14 38 253 G CA 489 399 −19 38 253 G C 503 404 −21 43 253 G O 505 413 −29 45 254 I N 513 399 −13 38 254 I CA 527 403 −13 38 254 I C 534 398 −25 41 254 I O 542 405 −31 41 254 I CB 534 399 0 41 254 I CG1 529 406 12 43 254 I CG2 549 401 −1 41 254 I CD1 534 420 14 60 255 I N 531 385 −29 36 255 I CA 536 379 −41 36 255 I C 530 387 −53 42 255 I O 536 389 −63 42 255 I CB 532 364 −42 40 255 I CG1 539 356 −31 41 255 I CG2 535 359 −56 38 255 I CD1 532 342 −29 43 256 S N 517 390 −52 42 256 S CA 511 398 −63 41 256 S C 518 412 −64 43 256 S O 521 416 −75 43 256 S CB 496 400 −61 44 256 S OG 489 388 −59 49 257 F N 520 418 −53 38 257 F CA 527 431 −53 36 257 F C 540 431 −61 40 257 F O 543 439 −69 39 257 F CB 530 436 −39 37 257 F CG 539 448 −38 38 257 F CD1 533 461 −41 39 257 F CD2 552 447 −33 39 257 F CE1 541 472 −40 40 257 F CE2 560 459 −32 41 257 F CZ 554 471 −35 38 258 A N 549 421 −58 39 258 A CA 562 419 −65 39 258 A C 561 417 −80 46 258 A O 568 423 −88 49 258 A CB 570 408 −58 39 259 K N 552 408 −83 42 259 K CA 549 405 −97 43 259 K C 546 417 −105 50 259 K O 550 418 −117 53 259 K CB 538 394 −98 41 259 K CG 541 380 −93 34 259 K CD 529 371 −92 44 259 K CE 520 374 −105 49 259 K NZ 509 364 −107 58 260 V N 538 426 −100 50 260 V CA 534 438 −109 52 260 V C 545 448 −112 57 260 V O 544 457 −120 59 260 V CB 522 445 −104 56 260 V CG1 513 437 −95 55 260 V CG2 526 458 −97 56 261 I N 556 447 −104 54 261 I CA 568 456 −106 54 261 I C 577 451 −117 58 261 I O 582 440 −116 56 261 I CB 576 457 −93 57 261 I CG1 566 460 −81 58 261 I CG2 587 467 −94 58 261 I CD1 573 458 −68 68 262 S N 579 459 −127 54 262 S CA 587 456 −139 53 262 S C 601 450 −135 58 262 S O 605 439 −139 59 262 S CB 589 468 −148 55 262 S OG 591 480 −140 63 263 Y N 608 458 −126 55 263 Y CA 621 454 −121 55 263 Y C 622 440 −115 55 263 Y O 632 434 −114 56 263 Y CB 626 465 −111 59 263 Y CG 627 478 −117 66 263 Y CD1 619 489 −112 67 263 Y CD2 635 481 −128 68 263 Y CE1 620 502 −118 69 263 Y CE2 636 493 −134 70 263 Y CZ 629 504 −129 81 263 Y OH 630 516 −135 87 264 F N 610 435 −110 49 264 F CA 610 422 −103 46 264 F C 607 411 −114 52 264 F O 614 401 −114 52 264 F CB 600 421 −92 46 264 F CG 600 408 −85 45 264 F CD1 608 406 −73 45 264 F CD2 591 398 −89 44 264 F CE1 607 395 −66 44 264 F CE2 591 386 −81 47 264 F CZ 599 384 −70 43 265 R N 598 414 −122 53 265 R CA 594 405 −133 54 265 R C 606 402 −143 60 265 R O 606 391 −149 62 265 R CB 582 411 −141 58 265 R CG 569 405 −137 62 265 R CD 558 410 −147 81 265 R NE 558 424 −150 84 265 R CZ 565 430 −160 101 265 R NH1 572 423 −168 96 265 R NH2 564 444 −161 74 266 D N 615 411 −144 57 266 D CA 627 409 −153 58 266 D C 638 401 −146 63 266 D O 649 399 −152 64 266 D CB 632 423 −158 59 266 D CG 622 431 −166 67 266 D OD1 612 425 −170 64 266 D OD2 624 443 −167 77 267 L N 635 397 −134 57 267 L CA 645 388 −127 56 267 L C 643 374 −131 59 267 L O 632 370 −135 61 267 L CB 643 390 −111 55 267 L CG 649 402 −104 58 267 L CD1 647 400 −89 57 267 L CD2 664 405 −107 57 268 P N 653 365 −129 56 268 P CA 651 351 −132 57 268 P C 642 345 −121 62 268 P O 643 349 −110 62 268 P CB 666 345 −130 58 268 P CG 675 357 −126 61 268 P CD 667 370 −130 57 269 I N 634 336 −125 59 269 I CA 624 330 −116 59 269 I C 630 325 −103 65 269 I O 623 325 −93 65 269 I CB 616 318 −122 62 269 I CG1 603 316 −115 62 269 I CG2 624 305 −122 64 269 I CD1 591 323 −121 67 270 E N 643 321 −103 61 270 E CA 649 316 −91 61 270 E C 652 327 −81 63 270 E O 653 325 −69 62 270 E CB 662 308 −94 62 270 E CG 659 294 −100 73 270 E CD 658 295 −115 103 270 E OE1 664 305 −121 98 270 E OE2 650 288 −121 104 271 D N 655 339 −87 56 271 D CA 657 350 −78 55 271 D C 644 355 −73 55 271 D O 643 358 −62 54 271 D CB 665 361 −86 57 271 D CG 680 358 −85 61 271 D OD1 688 367 −90 61 271 D OD2 684 347 −81 66 272 Q N 634 356 −82 48 272 Q CA 620 360 −78 47 272 Q C 616 352 −66 53 272 Q O 612 358 −56 51 272 Q CB 611 358 −90 48 272 Q CG 612 368 −101 52 272 Q CD 602 366 −112 64 272 Q OE1 604 372 −123 62 272 Q NE2 592 359 −109 64 273 I N 619 339 −66 52 273 I CA 616 331 −55 51 273 I C 624 334 −42 55 273 I O 619 336 −31 52 273 I CB 619 316 −58 54 273 I CG1 607 310 −66 56 273 I CG2 622 307 −46 54 273 I CD1 612 301 −77 62 274 S N 637 335 −44 51 274 S CA 647 338 −33 50 274 S C 644 351 −26 50 274 S O 645 352 −13 50 274 S CB 661 338 −38 53 274 S OG 665 325 −43 64 275 L N 640 362 −33 44 275 L CA 637 375 −28 44 275 L C 624 374 −20 47 275 L O 623 379 −9 46 275 L CB 636 385 −40 43 275 L CG 648 389 −47 47 275 L CD1 646 400 −56 46 275 L CD2 660 393 −36 48 276 L N 614 366 −25 42 276 L CA 601 364 −19 42 276 L C 602 356 −6 45 276 L O 596 361 4 43 276 L CB 591 358 −29 42 276 L CG 584 368 −37 46 276 L CD1 575 362 −49 45 276 L CD2 576 377 −29 39 277 K N 610 346 −6 44 277 K CA 612 338 7 43 277 K C 620 347 17 47 277 K O 618 346 29 49 277 K CB 621 326 5 44 277 K CG 619 318 −8 54 277 K CD 623 303 −6 71 277 K CE 635 302 3 67 277 K NZ 632 295 16 67 278 G N 628 356 12 44 278 G CA 636 365 20 44 278 G C 628 376 27 48 278 G O 629 379 39 49 279 A N 619 382 19 43 279 A CA 611 394 24 42 279 A C 596 392 28 46 279 A O 590 402 33 47 279 A CB 613 406 14 42 280 A N 590 381 25 39 280 A CA 576 379 27 40 280 A C 571 384 41 44 280 A O 561 391 42 45 280 A CB 573 364 25 41 281 F N 577 379 52 41 281 F CA 574 383 65 41 281 F C 575 398 67 40 281 F O 566 405 72 38 281 F CB 583 376 75 43 281 F CG 581 379 89 45 281 F CD1 571 373 97 46 281 F CD2 589 389 95 46 281 F CE1 569 377 110 44 281 F CE2 587 393 109 48 281 F CZ 577 386 116 43 282 E N 587 403 64 36 282 E CA 589 418 65 35 282 E C 579 426 57 39 282 E O 574 436 63 40 282 E CB 603 420 59 36 282 E CG 614 413 66 37 282 E CD 628 416 60 50 282 E OE1 629 426 52 39 282 E OE2 637 408 62 43 283 L N 576 423 45 37 283 L CA 566 430 37 37 283 L C 552 429 44 40 283 L O 543 438 43 36 283 L CB 565 426 23 37 283 L CG 577 430 13 42 283 L CD1 571 438 2 43 283 L CD2 587 438 19 40 284 C N 549 417 50 35 284 C CA 536 415 57 37 284 C C 535 424 68 42 284 C O 525 432 70 42 284 C CB 535 400 62 39 284 C SG 519 396 69 44 285 Q N 546 425 76 37 285 Q CA 546 434 88 38 285 Q C 545 449 84 42 285 Q O 537 457 90 44 285 Q CB 559 432 95 39 285 Q CG 560 418 102 41 285 Q CD 547 415 110 52 285 Q OE1 542 424 117 42 285 Q NE2 542 403 109 51 286 L N 552 453 73 35 286 L CA 550 467 68 34 286 L C 535 471 65 38 286 L O 530 481 69 38 286 L CB 559 471 56 34 286 L CG 574 471 60 37 286 L CD1 584 471 48 35 286 L CD2 577 482 69 38 287 R N 529 462 58 34 287 R CA 515 463 55 34 287 R C 505 463 67 38 287 R O 496 471 67 35 287 R CB 510 452 45 37 287 R CG 515 455 31 38 287 R CD 509 445 20 36 287 R NE 513 450 7 35 287 R CZ 507 446 −5 48 287 R NH1 498 437 −5 29 287 R NH2 512 451 −16 39 288 F N 508 454 76 35 288 F CA 500 453 89 36 288 F C 502 465 97 36 288 F O 493 470 104 37 288 F CB 504 441 97 39 288 F CG 496 428 95 42 288 F CD1 503 416 95 48 288 F CD2 483 428 92 46 288 F CE1 495 404 92 49 288 F CE2 476 417 89 50 288 F CZ 482 405 89 48 289 N N 513 471 96 32 289 N CA 515 484 103 31 289 N C 506 495 99 36 289 N O 502 503 106 42 289 N CB 530 489 102 27 289 N CG 533 499 113 39 289 N OD1 536 511 110 35 289 N ND2 534 495 125 34 290 T N 502 495 86 32 290 T CA 494 506 81 31 290 T C 479 506 86 36 290 T O 472 515 85 38 290 T CB 493 506 65 34 290 T OG1 487 494 60 38 290 T CG2 507 507 59 26 291 V N 475 494 91 33 291 V CA 462 492 97 33 291 V C 463 491 112 40 291 V O 454 486 119 41 291 V CB 455 480 91 37 291 V CG1 454 480 76 35 291 V CG2 463 467 95 36 292 F N 474 494 118 37 292 F CA 477 493 132 36 292 F C 472 506 139 43 292 F O 477 516 135 39 292 F CB 491 491 135 37 292 F CG 494 489 150 38 292 F CD1 488 478 157 37 292 F CD2 503 497 157 40 292 F CE1 491 475 170 37 292 F CE2 506 495 170 41 292 F CZ 499 484 177 37 293 N N 463 504 148 41 293 N CA 458 515 156 41 293 N C 466 515 169 49 293 N O 465 506 178 47 293 N CB 444 513 159 46 293 N CG 437 525 167 61 293 N OD1 445 532 174 51 293 N ND2 424 527 165 48 294 A N 476 524 171 48 294 A CA 485 524 182 49 294 A C 478 529 195 58 294 A O 482 526 206 59 294 A CB 498 532 180 48 295 E N 467 536 193 56 295 E CA 460 541 205 56 295 E C 453 530 212 60 295 E O 454 529 224 60 295 E CB 449 551 200 59 295 E CG 453 559 187 72 295 E CD 464 569 189 97 295 E OE1 471 572 179 97 295 E OE2 467 573 201 91 296 T N 446 521 204 54 296 T CA 439 510 209 51 296 T C 447 496 209 55 296 T O 441 486 213 54 296 T CB 426 508 202 56 296 T OG1 429 505 188 65 296 T CG2 417 520 203 46 297 G N 459 497 204 51 297 G CA 467 484 204 49 297 G C 461 473 195 51 297 G O 463 461 198 48 298 T N 454 477 184 47 298 T CA 448 468 176 46 298 T C 450 470 161 50 298 T O 451 481 156 53 298 T CB 432 466 180 53 298 T OG1 424 472 170 50 298 T CG2 429 473 193 47 299 W N 451 459 154 45 299 W CA 452 459 139 44 299 W C 437 458 134 46 299 W O 431 448 136 48 299 W CB 460 447 134 42 299 W CG 475 448 137 44 299 W CD1 485 454 130 47 299 W CD2 481 442 149 44 299 W NE1 497 453 137 45 299 W CE2 494 446 149 47 299 W CE3 476 436 160 46 299 W CZ2 503 442 159 48 299 W CZ3 485 432 171 48 299 W CH2 498 435 170 49 300 E N 433 468 127 42 300 E CA 420 468 121 42 300 E C 419 464 107 44 300 E O 421 471 97 40 300 E CB 414 482 123 43 300 E CG 417 488 137 61 300 E CD 413 502 138 74 300 E OE1 407 508 129 67 300 E OE2 415 508 149 66 301 C N 417 451 105 41 301 C CA 416 444 92 40 301 C C 402 442 87 46 301 C O 397 431 85 48 301 C CB 423 430 93 40 301 C SG 439 431 101 43 302 G N 396 453 83 44 302 G CA 383 452 77 46 302 G C 373 448 87 52 302 G O 372 453 98 53 303 R N 366 437 85 50 303 R CA 356 432 94 52 303 R C 362 424 106 56 303 R O 355 421 116 56 303 R CB 344 424 87 53 303 R CG 333 433 83 63 303 R CD 325 429 70 75 303 R NE 315 439 66 95 303 R CZ 312 442 53 119 303 R NH1 318 436 43 112 303 R NH2 303 452 51 102 304 L N 375 422 105 51 304 L CA 383 415 115 49 304 L C 392 425 123 47 304 L O 399 433 117 44 304 L CB 393 405 109 49 304 L CG 388 390 107 56 304 L CD1 397 383 97 56 304 L CD2 387 383 120 62 305 S N 393 423 136 40 305 S CA 402 432 145 39 305 S C 409 422 154 46 305 S O 404 413 160 43 305 S CB 394 441 153 40 305 S OG 387 451 146 58 306 Y N 422 425 156 44 306 Y CA 431 418 165 43 306 Y C 435 427 176 49 306 Y O 443 437 173 46 306 Y CB 443 412 158 42 306 Y CG 439 403 146 44 306 Y CD1 439 408 133 46 306 Y CD2 435 390 148 45 306 Y CE1 435 401 122 43 306 Y CE2 431 382 137 45 306 Y CZ 431 388 124 50 306 Y OH 428 381 113 51 307 C N 431 425 188 52 307 C CA 434 434 199 53 307 C C 444 428 208 58 307 C O 443 417 212 57 307 C CB 421 438 206 55 307 C SG 424 452 217 60 308 L N 454 436 211 58 308 L CA 465 432 221 58 308 L C 459 431 235 66 308 L O 453 441 239 66 308 L CB 476 442 220 57 308 L CG 490 437 215 61 308 L CD1 488 425 207 60 308 L CD2 497 448 208 60 309 E N 461 420 241 68 309 E CA 457 418 255 70 309 E C 465 426 265 80 309 E O 477 424 266 79 309 E CB 459 403 259 72 309 E CG 447 394 256 87 309 E CD 448 381 264 110 309 E OE1 459 377 268 106 309 E OE2 437 376 267 95 310 D N 458 435 272 80 310 D CA 466 444 282 82 310 D C 468 436 295 88 310 D O 459 429 300 88 310 D CB 458 457 285 84 310 D CG 464 468 276 100 310 D OD1 476 469 273 101 310 D OD2 455 477 272 108 311 T N 481 436 300 86 311 T CA 485 429 311 86 311 T C 493 437 321 89 311 T O 497 449 319 89 311 T CB 493 416 307 94 311 T OG1 507 420 306 93 311 T CG2 488 411 294 92 312 A N 497 431 332 86 312 A CA 505 437 343 85 312 A C 519 440 338 90 312 A O 525 431 331 92 312 A CB 506 427 355 86 313 G N 523 452 340 86 313 G CA 536 456 335 86 313 G C 534 468 326 88 313 G O 542 477 323 86 314 G N 521 468 320 83 314 G CA 517 479 311 82 314 G C 525 480 298 84 314 G O 530 470 293 82 315 F N 524 492 292 80 315 F CA 531 495 280 78 315 F C 545 490 280 82 315 F O 550 483 270 82 315 F CB 532 511 279 80 315 F CG 523 517 269 81 315 F CD1 523 513 256 84 315 F CD2 514 528 273 83 315 F CE1 514 520 247 85 315 F CE2 506 534 264 86 315 F CZ 505 530 251 83 316 Q N 552 492 291 78 316 Q CA 566 487 293 78 316 Q C 568 472 290 82 316 Q O 579 468 285 82 316 Q CB 571 491 307 79 316 Q CG 578 505 307 107 316 Q CD 573 513 295 130 316 Q OE1 562 516 293 129 316 Q NE2 583 517 286 118 317 Q N 559 464 295 78 317 Q CA 560 449 292 78 317 Q C 559 446 278 82 317 Q O 566 438 272 84 317 Q CB 550 441 301 80 317 Q CG 547 427 295 104 317 Q CD 543 417 306 134 317 Q OE1 540 406 303 134 317 Q NE2 542 422 318 124 318 L N 549 453 271 76 318 L CA 547 451 257 75 318 L C 559 455 248 76 318 L O 564 446 241 77 318 L CB 535 460 252 75 318 L CG 521 455 255 80 318 L CD1 511 466 251 80 318 L CD2 518 442 249 83 319 L N 565 467 250 69 319 L CA 576 471 243 68 319 L C 588 462 244 70 319 L O 598 463 236 70 319 L CB 580 485 247 68 319 L CG 571 497 243 73 319 L CD1 579 510 244 74 319 L CD2 566 495 228 73 320 L N 588 452 253 65 320 L CA 599 443 255 64 320 L C 599 433 244 66 320 L O 608 425 242 68 320 L CB 597 435 268 64 320 L CG 602 442 281 70 320 L CD1 616 435 285 70 320 L CD2 604 457 281 69 321 E N 587 432 237 58 321 E CA 586 422 226 57 321 E C 589 430 213 57 321 E O 583 440 209 57 321 E CB 571 418 226 58 321 E CG 568 408 214 70 321 E CD 576 396 215 96 321 E OE1 574 387 224 81 321 E OE2 585 394 206 101 322 P N 601 426 207 53 322 P CA 606 433 195 53 322 P C 597 436 184 55 322 P O 599 446 177 51 322 P CB 618 423 191 55 322 P CG 621 416 203 59 322 P CD 609 414 211 55 323 M N 587 427 181 54 323 M CA 578 430 170 53 323 M C 567 441 174 52 323 M O 563 448 166 51 323 M CB 571 417 166 57 323 M CG 566 417 151 62 323 M SD 579 423 140 68 323 M CE 571 436 130 64 324 L N 564 441 187 48 324 L CA 554 450 192 47 324 L C 560 464 193 48 324 L O 554 474 189 49 324 L CB 550 446 206 47 324 L CG 537 438 208 53 324 L CD1 531 433 194 53 324 L CD2 539 427 218 57 325 K N 573 465 197 41 325 K CA 580 478 197 41 325 K C 582 483 183 45 325 K O 578 495 180 45 325 K CB 594 476 204 42 325 K CG 601 489 204 69 325 K CD 613 488 214 83 325 K CE 624 499 212 94 325 K NZ 630 505 224 95 326 F N 586 474 174 42 326 F CA 587 478 159 41 326 F C 574 484 154 45 326 F O 575 495 149 46 326 F CB 592 466 151 44 326 F CG 592 469 136 47 326 F CD1 603 475 130 49 326 F CD2 580 467 128 51 326 F CE1 603 478 117 52 326 F CE2 580 470 115 55 326 F CZ 591 476 109 52 327 H N 563 478 157 42 327 H CA 550 484 153 44 327 H C 547 497 159 48 327 H O 543 507 152 49 327 H CB 538 473 155 47 327 H CG 536 464 144 53 327 H ND1 546 462 134 58 327 H CD2 527 455 140 57 327 H CE1 542 453 125 57 327 H NE2 530 448 129 56 328 Y N 550 499 172 42 328 Y CA 548 512 178 42 328 Y C 558 522 173 45 328 Y O 554 534 171 44 328 Y CB 548 510 194 44 328 Y CG 535 506 200 47 328 Y CD1 533 493 203 48 328 Y CD2 524 515 202 47 328 Y CE1 520 488 209 46 328 Y CE2 512 511 208 49 328 Y CZ 510 497 210 57 328 Y OH 498 493 215 62 329 M N 570 519 173 42 329 M CA 580 529 168 45 329 M C 578 533 153 46 329 M O 579 545 151 48 329 M CB 595 523 169 49 329 M CG 600 522 183 57 329 M SD 617 513 182 66 329 M CE 627 525 173 61 330 L N 573 524 145 38 330 L CA 571 528 131 36 330 L C 558 536 129 39 330 L O 558 545 120 36 330 L CB 570 515 122 35 330 L CG 569 517 107 39 330 L CD1 581 524 102 39 330 L CD2 568 503 100 40 331 K N 548 534 137 36 331 K CA 536 541 136 37 331 K C 538 555 140 42 331 K O 533 565 134 41 331 K CB 525 534 146 40 331 K CG 510 538 143 34 331 K CD 505 531 130 32 331 K CE 494 539 124 28 331 K NZ 486 532 113 47 332 K N 547 557 151 40 332 K CA 550 571 156 41 332 K C 557 579 145 47 332 K O 555 592 146 51 332 K CB 559 569 168 45 332 K CG 556 580 179 70 332 K CD 568 580 189 84 332 K CE 565 590 200 96 332 K NZ 571 586 213 107 333 L N 564 574 136 43 333 L CA 570 582 125 41 333 L C 560 588 116 45 333 L O 564 596 107 45 333 L CB 580 573 117 41 333 L CG 592 567 125 44 333 L CD1 601 559 115 40 333 L CD2 600 579 133 41 334 Q N 548 584 116 43 334 Q CA 537 588 107 44 334 Q C 541 589 92 48 334 Q O 540 600 87 50 334 Q CB 532 602 112 45 334 Q CG 526 601 126 60 334 Q CD 522 614 132 77 334 Q OE1 513 621 127 66 334 Q NE2 529 619 143 80 335 L N 545 578 87 40 335 L CA 549 578 73 38 335 L C 538 579 64 45 335 L O 527 575 67 46 335 L CB 557 564 70 36 335 L CG 568 561 79 39 335 L CD1 575 548 75 40 335 L CD2 578 572 79 42 336 H N 541 583 51 43 336 H CA 530 584 41 43 336 H C 530 570 34 43 336 H O 538 562 35 41 336 H CB 534 596 31 46 336 H CG 533 610 36 52 336 H ND1 542 620 34 54 336 H CD2 523 615 44 56 336 H CE1 538 631 40 55 336 H NE2 526 628 46 56 337 E N 519 568 26 37 337 E CA 518 556 18 36 337 E C 531 554 10 38 337 E O 537 544 9 33 337 E CB 506 557 9 39 337 E CG 493 559 16 46 337 E CD 486 546 21 59 337 E OE1 492 535 19 39 337 E OE2 476 547 28 48 338 E N 535 565 3 37 338 E CA 547 566 −5 37 338 E C 560 561 2 41 338 E O 567 553 −4 45 338 E CB 550 580 −11 38 338 E CG 540 584 −22 32 338 E CD 528 591 −16 47 338 E OE1 519 596 −24 62 338 E OE2 526 592 −3 43 339 E N 562 564 15 36 339 E CA 573 559 22 36 339 E C 572 545 26 38 339 E O 582 537 26 40 339 E CB 576 568 34 38 339 E CG 579 582 30 41 339 E CD 575 592 40 59 339 E OE1 566 590 48 44 339 E OE2 582 603 40 46 340 Y N 560 540 30 31 340 Y CA 558 526 33 31 340 Y C 561 518 20 33 340 Y O 568 507 21 35 340 Y CB 544 522 37 31 340 Y CG 541 525 51 32 340 Y CD1 533 535 56 32 340 Y CD2 546 516 61 29 340 Y CE1 530 538 69 34 340 Y CE2 544 518 75 28 340 Y CZ 535 529 78 32 340 Y OH 531 532 91 27 341 V N 556 522 9 26 341 V CA 558 514 −3 26 341 V C 572 513 −8 32 341 V O 576 503 −14 36 341 V CB 548 518 −14 31 341 V CG1 553 531 −22 29 341 V CG2 545 507 −24 32 342 L N 580 524 −5 30 342 L CA 594 524 −8 29 342 L C 602 515 2 32 342 L O 612 510 −2 32 342 L CB 599 538 −9 31 342 L CG 597 547 −21 35 342 L CD1 599 562 −17 34 342 L CD2 606 543 −33 31 343 M N 597 514 14 31 343 M CA 603 504 24 26 343 M C 601 491 19 33 343 M O 609 482 20 37 343 M CB 596 506 38 28 343 M CG 600 519 46 30 343 M SD 592 520 62 32 343 M CE 604 510 71 28 344 Q N 589 488 14 29 344 Q CA 586 475 9 29 344 Q C 595 471 −2 36 344 Q O 601 460 −2 37 344 Q CB 571 474 4 29 344 Q CG 561 472 15 20 344 Q CD 546 475 12 34 344 Q OE1 539 480 20 30 344 Q NE2 543 473 −1 36 345 A N 597 480 −12 36 345 A CA 606 478 −23 34 345 A C 621 476 −18 40 345 A O 627 467 −23 39 345 A CB 606 490 −32 34 346 I N 625 484 −9 38 346 I CA 639 482 −3 35 346 I C 641 469 3 38 346 I O 652 463 2 39 346 I CB 643 494 6 37 346 I CG1 643 507 −1 37 346 I CG2 656 491 13 33 346 I CD1 644 519 7 33 347 S N 631 464 11 36 347 S CA 632 451 17 34 347 S C 631 440 6 42 347 S O 638 430 6 43 347 S CB 622 449 28 41 347 S OG 616 436 29 44 348 L N 623 442 −4 40 348 L CA 621 432 −14 40 348 L C 634 430 −22 45 348 L O 639 418 −21 46 348 L CB 609 436 −24 39 348 L CG 606 425 −34 41 348 L CD1 603 412 −28 39 348 L CD2 595 429 −44 34 349 F N 639 440 −27 42 349 F CA 652 440 −35 41 349 F C 664 440 −26 47 349 F O 673 448 −28 47 349 F CB 652 452 −44 42 349 F CG 641 450 −55 43 349 F CD1 630 458 −55 45 349 F CD2 643 441 −66 43 349 F CE1 620 457 −65 46 349 F CE2 634 440 −76 46 349 F CZ 623 447 −75 44 350 S N 666 430 −17 46 350 S CA 677 428 −9 48 350 S C 687 418 −15 58 350 S O 684 406 −16 58 350 S CB 673 423 5 51 350 S OG 668 434 13 66 351 P N 699 423 −18 59 351 P CA 709 415 −25 60 351 P C 715 403 −17 66 351 P O 720 394 −22 66 351 P CB 720 425 −29 61 351 P CG 719 436 −19 66 351 P CD 704 437 −16 61 352 D N 714 405 −4 64 352 D CA 720 395 5 63 352 D C 711 384 11 66 352 D O 713 378 21 69 352 D CB 727 402 17 66 352 D CG 718 410 25 78 352 D OD1 706 409 24 77 352 D OD2 724 419 33 85 353 R N 700 380 3 61 353 R CA 691 370 7 60 353 R C 698 357 2 64 353 R O 703 357 −9 64 353 R CB 677 371 1 56 353 R CG 670 384 3 51 353 R CD 667 387 18 57 353 R NE 658 398 19 55 353 R CZ 653 402 31 62 353 R NH1 656 396 42 48 353 R NH2 644 412 32 42 354 P N 697 346 9 60 354 P CA 703 333 5 60 354 P C 697 329 −8 67 354 P O 685 330 −10 67 354 P CB 698 324 16 62 354 P CG 697 332 28 65 354 P CD 694 346 24 59 355 G N 705 324 −17 66 355 G CA 700 318 −30 66 355 G C 700 328 −42 70 355 G O 697 324 −53 70 356 V N 703 341 −39 65 356 V CA 702 351 −49 64 356 V C 715 351 −57 70 356 V O 726 353 −51 70 356 V CB 699 365 −44 67 356 V CG1 700 376 −54 66 356 V CG2 685 366 −37 66 357 L N 714 349 −70 68 357 L CA 726 349 −79 67 357 L C 729 363 −84 69 357 L O 741 366 −85 70 357 L CB 724 339 −91 67 357 L CG 721 324 −87 72 357 L CD1 717 315 −98 72 357 L CD2 732 318 −78 75 358 Q N 719 370 −88 63 358 Q CA 721 384 −93 61 358 Q C 723 395 −82 64 358 Q O 717 405 −83 63 358 Q CB 709 388 −102 61 358 Q CG 707 378 −113 63 358 Q CD 710 385 −126 95 358 Q OE1 720 382 −133 80 358 Q NE2 701 394 −130 98 359 H N 732 392 −72 61 359 H N 732 392 −72 60 359 H CA 734 402 −62 61 359 H CA 735 401 −62 60 359 H CB 746 399 −52 62 359 H CB 747 397 −54 61 359 H CG 760 400 −58 65 359 H CG 745 384 −46 64 359 H ND1 766 390 −64 67 359 H ND1 733 382 −38 66 359 H CE1 778 394 −68 66 359 H CE1 734 371 −32 66 359 H NE2 779 407 −66 66 359 H NE2 746 366 −35 66 359 H CD2 768 411 −60 67 359 H CD2 753 374 −43 66 359 H C 737 416 −67 67 359 H C 737 416 −67 66 359 H O 734 426 −60 68 359 H O 733 425 −60 67 360 R N 743 417 −78 63 360 R CA 747 430 −84 63 360 R C 735 439 −89 66 360 R O 735 450 −85 67 360 R CB 757 428 −95 68 360 R CG 764 441 −99 87 360 R CD 773 446 −88 110 360 R NE 781 457 −94 131 360 R CZ 787 467 −87 150 360 R NH1 786 467 −74 140 360 R NH2 794 476 −93 136 361 V N 727 433 −98 61 361 V CA 716 441 −103 61 361 V C 706 444 −92 63 361 V O 702 456 −91 61 361 V CB 708 432 −113 65 361 V CG1 694 437 −115 65 361 V CG2 716 431 −126 65 362 V N 704 434 −83 56 362 V CA 695 436 −71 55 362 V C 700 447 −62 60 362 V O 692 454 −56 60 362 V CB 693 423 −64 58 362 V CG1 685 424 −51 58 362 V CG2 686 412 −73 57 363 D N 713 449 −62 57 363 D CA 719 460 −53 56 363 D C 718 473 −60 59 363 D O 717 483 −53 60 363 D CB 734 456 −50 58 363 D CG 740 467 −42 66 363 D OD1 742 466 −30 65 363 D OD2 743 478 −48 74 364 Q N 719 474 −73 55 364 Q CA 717 487 −80 55 364 Q C 702 491 −78 56 364 Q O 700 503 −75 56 364 Q CB 719 485 −95 57 364 Q CG 730 475 −99 87 364 Q CD 744 479 −94 112 364 Q OE1 747 480 −83 112 364 Q NE2 752 482 −104 103 365 L N 693 482 −80 50 365 L CA 679 484 −77 50 365 L C 677 489 −63 53 365 L O 670 499 −61 53 365 L CB 671 471 −80 50 365 L CG 671 466 −95 54 365 L CD1 664 452 −96 55 365 L CD2 663 476 −103 52 366 Q N 682 481 −53 50 366 Q CA 680 485 −40 51 366 Q C 684 500 −37 57 366 Q O 677 507 −30 58 366 Q CB 686 476 −30 51 366 Q CG 681 478 −16 57 366 Q CD 689 470 −5 58 366 Q OE1 701 470 −5 48 366 Q NE2 682 464 4 46 367 E N 696 503 −43 51 367 E CA 702 517 −41 50 367 E C 693 528 −47 53 367 E O 693 539 −42 53 367 E CB 716 517 −45 52 367 E CG 722 532 −45 67 367 E CD 736 532 −48 88 367 E OE1 744 539 −40 95 367 E OE2 740 526 −58 71 368 Q N 687 525 −58 47 368 Q CA 678 535 −65 45 368 Q C 665 537 −57 45 368 Q O 660 548 −56 45 368 Q CB 675 531 −79 47 368 Q CG 687 532 −89 60 368 Q CD 696 544 −86 85 368 Q OE1 691 556 −86 80 368 Q NE2 709 542 −84 80 369 F N 660 526 −51 39 369 F CA 648 528 −42 36 369 F C 651 536 −30 43 369 F O 644 545 −26 41 369 F CB 642 514 −38 37 369 F CG 635 507 −50 37 369 F CD1 639 494 −54 37 369 F CD2 624 513 −56 37 369 F CE1 633 488 −64 37 369 F CE2 618 506 −67 39 369 F CZ 623 494 −70 36 370 A N 663 533 −24 38 370 A CA 668 540 −12 38 370 A C 670 555 −16 45 370 A O 666 564 −8 45 370 A CB 680 534 −8 38 371 I N 677 558 −27 42 371 I CA 679 571 −31 42 371 I C 666 579 −34 46 371 I O 665 590 −30 47 371 I CB 688 571 −44 46 371 I CG1 702 570 −41 44 371 I CG2 685 584 −53 47 371 I CD1 710 565 −52 52 372 T N 656 572 −40 42 372 T CA 643 578 −43 41 372 T C 636 582 −30 44 372 T O 629 592 −29 43 372 T CB 634 569 −51 44 372 T OG1 639 566 −64 49 372 T CG2 621 576 −53 47 373 L N 638 573 −20 42 373 L CA 631 575 −7 41 373 L C 638 587 0 44 373 L O 631 596 5 41 373 L CB 633 562 1 40 373 L CG 628 563 15 45 373 L CD1 613 566 15 45 373 L CD2 631 550 23 40 374 K N 651 588 0 42 374 K CA 658 599 5 42 374 K C 653 613 −1 47 374 K O 652 623 6 47 374 K CB 673 598 3 44 374 K CG 681 608 10 45 374 K CD 696 606 8 42 374 K CE 703 616 16 44 374 K NZ 716 620 10 72 375 S N 651 613 −14 45 375 S CA 647 625 −21 46 375 S C 632 628 −18 52 375 S O 628 640 −17 52 375 S CB 648 623 −36 51 375 S OG 661 620 −41 62 376 Y N 623 618 −18 49 376 Y CA 609 620 −16 48 376 Y C 608 627 −2 47 376 Y O 601 636 0 47 376 Y CB 601 607 −16 49 376 Y CG 587 609 −11 49 376 Y CD1 584 610 3 49 376 Y CD2 576 611 −20 50 376 Y CE1 571 613 7 47 376 Y CE2 563 614 −15 50 376 Y CZ 561 615 −2 54 376 Y OH 549 617 3 59 377 I N 616 622 8 41 377 I CA 615 628 21 40 377 I C 620 642 22 51 377 I O 615 650 30 52 377 I CB 624 619 31 41 377 I CG1 616 606 35 40 377 I CG2 626 627 44 37 377 I CD1 624 596 42 36 378 E N 629 646 13 52 378 E CA 634 659 12 53 378 E C 625 669 6 61 378 E O 624 680 10 63 378 E CB 648 659 5 53 378 E CG 660 659 14 52 378 E CD 672 652 9 87 378 E OE1 676 655 −2 80 378 E OE2 677 643 17 95 379 C N 618 664 −4 61 379 C CA 608 672 −11 63 379 C C 595 674 −4 70 379 C O 586 682 −8 74 379 C CB 605 666 −25 63 379 C SG 620 665 −35 68 380 N N 593 667 7 64 380 N CA 580 667 14 62 380 N C 580 668 29 65 380 N O 569 670 35 64 380 N CB 571 655 9 57 380 N CG 570 654 −6 73 380 N OD1 561 659 −12 77 380 N ND2 580 647 −12 52 381 R N 591 668 36 62 381 R CA 592 668 50 62 381 R C 602 678 57 69 381 R O 610 674 65 67 381 R CB 593 654 56 61 381 R CG 589 643 47 61 381 R CD 582 631 54 52 381 R NE 572 635 63 60 381 R CZ 563 628 68 62 381 R NH1 563 615 66 33 381 R NH2 554 633 77 66 382 P N 600 691 54 69 382 P CA 609 701 60 69 382 P C 609 704 75 73 382 P O 616 713 80 72 382 P CB 605 714 52 71 382 P CG 590 712 50 74 382 P CD 587 697 50 69 383 Q N 600 697 82 69 383 Q CA 598 700 96 68 383 Q C 608 695 106 74 383 Q O 615 685 104 74 383 Q CB 584 696 100 70 383 Q CG 573 706 95 94 383 Q CD 567 702 82 116 383 Q OE1 564 690 80 107 383 Q NE2 567 711 73 118 384 P N 608 702 118 73 384 P CA 617 699 129 72 384 P C 614 685 134 77 384 P O 622 678 140 78 384 P CB 613 709 139 74 384 P CG 610 722 131 78 384 P CD 604 716 118 74 385 A N 601 681 132 72 385 A CA 597 668 137 69 385 A C 603 656 128 72 385 A O 606 646 134 74 385 A CB 582 667 136 70 386 H N 605 659 115 64 386 H CA 610 648 106 62 386 H C 625 648 103 58 386 H O 629 643 92 56 386 H CB 602 648 94 63 386 H CG 587 652 96 68 386 H ND1 580 660 87 70 386 H CD2 578 648 105 70 386 H CE1 568 661 91 70 386 H NE2 566 655 102 71 387 R N 634 652 112 49 387 R CA 648 652 110 45 387 R C 654 638 111 45 387 R O 651 631 120 46 387 R CB 656 661 120 41 387 R CG 658 675 115 40 387 R CD 662 684 126 41 387 R NE 677 683 128 31 387 R CZ 684 689 137 44 387 R NH1 678 696 147 32 387 R NH2 697 687 138 22 388 F N 663 635 102 37 388 F CA 669 621 102 36 388 F C 660 610 98 38 388 F O 663 598 99 37 388 F CB 676 618 115 37 388 F CG 686 629 120 39 388 F CD1 683 635 133 39 388 F CD2 697 632 114 41 388 F CE1 691 644 138 39 388 F CE2 706 642 119 43 388 F CZ 703 648 131 40 389 L N 648 614 93 37 389 L CA 638 604 89 39 389 L C 643 593 80 43 389 L O 641 581 83 46 389 L CB 625 610 83 39 389 L CG 613 601 81 44 389 L CD1 610 594 95 41 389 L CD2 601 609 76 44 390 F N 650 596 70 38 390 F CA 654 586 60 40 390 F C 663 576 67 41 390 F O 662 564 65 43 390 F CB 662 593 49 41 390 F CG 669 583 40 43 390 F CD1 663 575 31 45 390 F CD2 683 582 41 44 390 F CE1 669 565 23 46 390 F CE2 690 572 33 46 390 F CZ 683 564 24 44 391 L N 672 581 76 36 391 L CA 682 572 83 35 391 L C 674 564 94 39 391 L O 678 554 98 42 391 L CB 693 581 90 35 391 L CG 703 588 81 41 391 L CD1 710 599 88 37 391 L CD2 712 578 74 43 392 K N 663 570 100 35 392 K CA 656 562 110 35 392 K C 649 550 103 38 392 K O 650 539 106 38 392 K CB 646 571 117 37 392 K CG 652 583 124 39 392 K CD 644 586 137 46 392 K CE 643 601 139 62 392 K NZ 630 605 141 80 393 I N 643 554 92 34 393 I CA 636 544 83 34 393 I C 645 533 79 40 393 I O 642 521 80 43 393 I CB 630 550 70 36 393 I CG1 617 558 74 35 393 I CG2 627 539 60 38 393 I CD1 610 566 61 29 394 M N 657 536 75 38 394 M CA 667 526 71 38 394 M C 672 517 82 42 394 M O 674 506 81 40 394 M CB 679 532 63 40 394 M CG 675 539 50 43 394 M SD 668 529 37 46 394 M CE 682 518 34 42 395 A N 673 523 94 42 395 A CA 677 516 106 42 395 A C 665 506 110 45 395 A O 668 495 114 48 395 A CB 681 525 118 42 396 M N 653 510 109 41 396 M CA 641 502 111 42 396 M C 641 490 102 43 396 M O 638 479 106 43 396 M CB 629 510 110 45 396 M CG 630 523 117 51 396 M SD 619 524 130 58 396 M CE 620 507 137 52 397 L N 645 491 90 38 397 L CA 645 480 80 38 397 L C 656 470 84 46 397 L O 654 458 83 49 397 L CB 649 486 66 38 397 L CG 637 492 58 39 397 L CD1 642 497 44 37 397 L CD2 626 482 56 34 398 T N 667 475 90 42 398 T CA 677 466 95 41 398 T C 673 459 108 46 398 T O 676 448 110 48 398 T CB 691 474 98 54 398 T OG1 696 479 86 49 398 T CG2 701 464 104 58 399 E N 664 466 116 42 399 E CA 658 459 127 43 399 E CB 651 469 136 45 399 E C 648 448 122 49 399 E O 650 436 125 52 400 L N 639 452 113 43 400 L CA 629 443 107 42 400 L C 635 430 102 47 400 L O 630 419 104 44 400 L CB 621 450 96 40 400 L CG 609 442 91 44 400 L CD1 601 436 103 41 400 L CD2 600 450 82 43 401 R N 647 431 96 45 401 R N 647 431 96 45 401 R CA 654 419 91 46 401 R CA 654 419 91 46 401 R CB 665 424 82 44 401 R CB 665 422 81 45 401 R CG 671 413 73 54 401 R CG 669 410 73 57 401 R CD 685 416 69 59 401 R CD 678 415 61 62 401 R NE 690 404 62 61 401 R NE 687 426 65 77 401 R CZ 693 405 49 61 401 R CZ 700 425 66 87 401 R NH1 693 416 42 34 401 R NH1 706 414 64 67 401 R NH2 698 394 43 50 401 R NH2 707 436 70 70 401 R C 659 410 102 52 401 R C 659 410 102 52 401 R O 660 398 100 53 401 R O 660 398 101 53 402 S N 662 416 114 49 402 S CA 667 408 125 49 402 S C 654 402 132 52 402 S O 654 390 135 53 402 S CB 675 416 135 52 402 S OG 675 410 148 73 403 I N 643 409 132 47 403 I CA 631 404 138 47 403 I C 625 392 130 50 403 I O 621 382 135 49 403 I CB 620 415 140 48 403 I CG1 624 425 151 46 403 I CG2 607 409 141 46 403 I CD1 617 438 150 52 404 N N 627 394 117 49 404 N CA 624 383 107 50 404 N C 630 370 110 57 404 N O 624 359 108 58 404 N CB 628 388 93 47 404 N CG 626 378 82 63 404 N OD1 616 370 83 47 404 N ND2 634 379 72 74 405 A N 643 370 113 56 405 A CA 650 358 116 57 405 A C 646 352 130 62 405 A O 646 340 131 63 405 A CB 665 360 116 57 406 Q N 643 361 139 61 406 Q CA 638 356 152 62 406 Q C 624 350 152 66 406 Q O 621 341 159 67 406 Q CB 639 368 162 64 406 Q CG 641 364 176 86 406 Q CD 628 367 185 111 406 Q OE1 621 377 183 104 406 Q NE2 626 358 194 108 407 H N 616 355 142 63 407 H CA 602 349 141 64 407 H C 602 336 133 65 407 H O 594 328 134 63 407 H CB 592 359 134 65 407 H CG 583 365 144 70 407 H ND1 570 361 146 72 407 H CD2 585 376 153 72 407 H CE1 565 368 156 72 407 H NE2 573 377 160 72 408 T N 612 335 124 61 408 T CA 614 322 116 61 408 T C 619 311 125 64 408 T O 616 299 122 63 408 T CB 623 325 104 65 408 T OG1 617 335 95 65 408 T CG2 624 312 96 54 409 Q N 626 315 136 61 409 Q N 625 315 136 61 409 Q CA 630 305 145 60 409 Q CA 631 305 145 60 409 Q CB 643 310 153 61 409 Q CB 642 311 153 62 409 Q CG 655 311 144 63 409 Q CG 655 312 146 71 409 Q CD 662 298 140 81 409 Q CD 664 324 150 93 409 Q OE1 664 289 149 77 409 Q OE1 663 329 161 92 409 Q NE2 665 297 128 74 409 Q NE2 672 329 140 79 409 Q C 619 300 154 63 409 Q C 619 301 154 64 409 Q O 617 289 157 66 409 Q O 617 289 156 66 410 R N 611 310 159 58 410 R CA 599 307 167 57 410 R C 590 298 159 60 410 R O 586 288 164 61 410 R CB 592 320 171 56 410 R CG 598 328 181 55 410 R CD 588 339 186 70 410 R NE 595 351 190 78 410 R CZ 590 360 198 88 410 R NH1 578 358 204 85 410 R NH2 597 371 202 69 411 L N 588 301 147 56 411 L CA 579 294 138 58 411 L C 582 279 137 63 411 L O 573 271 137 62 411 L CB 579 300 124 57 411 L CG 566 299 116 63 411 L CD1 560 285 117 63 411 L CD2 556 309 123 67 412 L N 595 277 134 60 412 L CA 600 263 132 60 412 L C 598 255 145 64 412 L O 594 244 145 64 412 L CB 614 263 127 61 412 L CG 616 272 115 65 412 L CD1 630 270 109 66 412 L CD2 605 269 105 68 413 R N 601 262 156 61 413 R CA 599 255 169 61 413 R C 585 251 171 67 413 R O 582 239 172 68 413 R CB 603 265 181 58 413 R CG 617 265 185 60 413 R CD 620 274 196 68 413 R NE 629 285 192 83 413 R CZ 628 297 195 94 413 R NH1 619 302 203 84 413 R NH2 638 306 190 72 414 I N 576 260 170 61 414 I CA 562 257 172 61 414 I C 557 246 163 66 414 I O 551 236 166 68 414 I CB 552 269 169 63 414 I CG1 557 281 178 63 414 I CG2 538 266 172 63 414 I CD1 556 294 170 66 415 Q N 562 247 150 62 415 Q CA 558 237 140 62 415 Q C 562 223 142 69 415 Q O 556 214 137 67 415 Q CB 562 243 126 62 415 Q CG 559 233 115 48 415 Q CD 545 235 109 69 415 Q OE1 537 242 114 60 415 Q NE2 543 228 98 59 416 D N 573 221 149 70 416 D CA 578 208 152 72 416 D C 568 201 162 77 416 D O 564 190 159 77 416 D CB 591 209 160 75 416 D CG 598 196 162 95 416 D OD1 605 195 173 96 416 D OD2 597 187 153 107 417 I N 564 208 173 73 417 I CA 555 203 183 73 417 I C 541 204 179 77 417 I O 533 196 184 77 417 I CB 556 213 195 76 417 I CG1 570 212 202 77 417 I CG2 544 211 204 78 417 I CD1 573 225 209 85 418 H N 538 213 170 71 418 H CA 524 215 166 71 418 H C 523 220 151 73 418 H O 522 232 149 73 418 H CB 517 225 175 71 418 H CG 502 224 176 74 418 H ND1 494 234 171 76 418 H CD2 494 214 181 76 418 H CE1 481 230 173 76 418 H NE2 481 219 179 76 419 P N 522 211 141 69 419 P CA 521 216 127 68 419 P C 508 224 125 70 419 P O 497 219 126 69 419 P CB 520 202 120 70 419 P CG 529 193 128 74 419 P CD 529 198 142 70 420 F N 510 236 120 63 420 F CA 498 245 117 61 420 F C 500 253 104 65 420 F O 491 258 98 66 420 F CB 496 255 128 62 420 F CG 506 265 129 62 420 F CD1 505 277 122 65 420 F CD2 518 263 136 62 420 F CE1 515 287 123 65 420 F CE2 528 272 137 65 420 F CZ 527 284 130 63 421 A N 513 253 99 60 421 A CA 516 260 87 60 421 A C 510 256 74 64 421 A O 510 244 71 67 421 A CB 532 262 85 60 422 T N 505 265 66 60 422 T CA 499 262 53 58 422 T C 510 258 43 62 422 T O 522 260 45 60 422 T CB 492 275 48 62 422 T OG1 501 285 48 58 422 T CG2 480 278 57 60 423 P N 506 251 33 59 423 P CA 516 246 23 58 423 P C 524 259 18 59 423 P O 536 258 16 59 423 P CB 507 241 11 59 423 P CG 495 236 18 64 423 P CD 493 245 30 59 424 L N 517 270 16 52 424 L CA 525 282 12 51 424 L C 534 288 22 56 424 L O 545 293 18 57 424 L CB 515 293 5 51 424 L CG 523 306 2 54 424 L CD1 536 303 −6 52 424 L CD2 514 316 −3 46 425 M N 531 287 35 51 425 M CA 541 291 45 50 425 M C 552 282 46 56 425 M O 564 286 49 58 425 M CB 534 292 59 52 425 M CG 525 304 61 55 425 M SD 515 301 76 57 425 M CE 526 305 89 52 426 Q N 550 269 44 55 426 Q CA 561 259 45 55 426 O C 571 261 34 55 426 Q O 583 260 36 55 426 Q CB 556 244 44 56 426 Q CG 545 240 55 69 426 Q CD 538 227 50 82 426 Q OE1 544 217 47 72 426 Q NE2 524 228 50 81 427 E N 567 266 23 50 427 E CA 576 269 12 50 427 E C 584 281 15 55 427 E O 596 281 14 55 427 E CB 568 271 −2 51 427 E CG 563 258 −8 59 427 E CD 557 260 −21 71 427 E OE1 560 270 −28 59 427 E OE2 547 252 −25 60 428 L N 578 292 19 54 428 L CA 585 305 22 54 428 L C 595 303 34 62 428 L O 605 310 34 62 428 L CB 575 316 26 53 428 L CG 565 321 16 59 428 L CD1 556 332 22 59 428 L CD2 572 327 4 55 429 F N 591 295 44 62 429 F CA 600 293 55 64 429 F C 609 281 55 71 429 F O 619 281 63 72 429 F CB 592 294 68 67 429 F CG 583 306 69 68 429 F CD1 570 305 74 73 429 F CD2 588 318 65 71 429 F CE1 562 316 75 75 429 F CE2 580 329 66 74 429 F CZ 567 329 70 73 430 G N 607 272 45 71 430 G CA 615 260 44 72 430 G C 612 250 55 79 430 G O 619 250 65 78 431 I N 602 241 52 77 431 I CA 598 231 62 78 431 I C 595 218 56 84 431 I O 588 216 46 85 431 I CB 585 236 70 80 431 I CG1 589 247 80 79 431 I CG2 578 225 77 81 431 I CD1 578 257 82 82 444 S N 675 245 −90 86 444 S CA 664 235 −86 85 444 S C 654 241 −76 87 444 S O 646 234 −70 87 444 S CB 670 222 −81 90 444 S OG 665 217 −69 98 445 L N 655 254 −73 82 445 L CA 646 261 −64 80 445 L C 631 258 −67 82 445 L O 623 256 −58 81 445 L CB 648 276 −64 79 445 L CG 660 281 −56 83 445 L CD1 664 295 −61 83 445 L CD2 657 281 −41 86 446 T N 628 259 −80 78 446 T CA 614 257 −85 77 446 T C 607 244 −80 80 446 T O 595 244 −78 79 446 T CB 613 258 −100 85 446 T OG1 622 248 −106 89 446 T CG2 616 272 −106 81 447 E N 615 234 −78 76 447 E CA 610 221 −74 76 447 E C 606 221 −60 79 447 E O 595 216 −56 80 447 E CB 621 210 −76 78 447 E CG 616 197 −82 88 447 E CD 627 189 −90 103 447 E OE1 639 194 −89 89 447 E OE2 624 179 −96 88 448 R N 614 227 −51 74 448 R CA 611 227 −37 75 448 R C 601 238 −32 77 448 R O 599 240 −20 76 448 R CB 624 228 −29 79 448 R CG 635 219 −35 93 448 R CD 647 218 −26 109 448 R NE 657 227 −31 127 448 R CZ 659 240 −28 146 448 R NH1 668 247 −34 136 448 R NH2 650 245 −19 134 449 H N 595 245 −42 71 449 H CA 584 255 −40 71 449 H C 575 255 −51 70 449 H O 574 265 −59 68 449 H CB 590 269 −39 73 449 H CG 603 271 −32 77 449 H ND1 603 271 −18 80 449 H CD2 615 271 −37 80 449 H CE1 616 271 −15 79 449 H NE2 623 271 −26 79 450 K N 567 244 −53 65 450 K CA 558 243 −64 64 450 K C 547 254 −64 66 450 K O 542 257 −75 66 450 K CB 552 229 −65 68 450 K CG 561 218 −59 94 450 K CD 553 204 −59 107 450 K CE 560 194 −69 125 450 K NZ 555 180 −67 131 451 I N 543 259 −52 60 451 I CA 532 269 −52 58 451 I C 537 282 −56 58 451 I O 530 289 −64 57 451 I CB 526 270 −38 61 451 I CG1 521 256 −33 61 451 I CG2 515 280 −37 60 451 I CD1 517 256 −18 59 452 L N 548 287 −51 54 452 L CA 554 300 −55 53 452 L C 556 301 −70 59 452 L O 553 311 −76 58 452 L CB 567 302 −48 53 452 L CG 567 311 −35 57 452 L CD1 581 311 −29 54 452 L CD2 562 325 −40 57 453 H N 562 290 −75 58 453 H CA 564 289 −90 57 453 H C 552 291 −98 54 453 H O 551 299 −107 54 453 H CB 571 275 −93 60 453 H CG 576 274 −107 65 453 H ND1 587 281 −111 67 453 H CD2 570 269 −118 68 453 H CE1 588 279 −124 67 453 H NE2 578 271 −129 67 454 R N 541 284 −94 45 454 R CA 528 286 −100 44 454 R C 523 300 −100 49 454 R O 519 306 −110 50 454 R CB 518 276 −94 42 454 R CG 505 274 −102 51 454 R CD 494 267 −94 58 454 R NE 486 277 −86 74 454 R CZ 484 276 −73 81 454 R NH1 490 267 −66 74 454 R NH2 477 286 −67 57 455 L N 523 306 −87 47 455 L CA 518 319 −85 46 455 L C 526 329 −94 50 455 L O 520 338 −101 50 455 L CB 520 323 −70 45 455 L CG 511 315 −61 49 455 L CD1 512 320 −46 47 455 L CD2 497 315 −65 48 456 L N 539 327 −95 47 456 L CA 548 336 −103 48 456 L C 546 335 −118 53 456 L O 548 344 −126 50 456 L CB 563 334 −100 48 456 L CG 567 339 −86 51 456 L CD1 581 336 −83 50 456 L CD2 564 354 −85 51 457 Q N 541 323 −122 51 457 Q CA 538 321 −136 51 457 Q C 525 327 −141 54 457 Q O 523 331 −152 53 457 Q CB 539 306 −140 52 457 Q CG 553 301 −143 57 457 Q CD 552 287 −148 77 457 Q OE1 556 277 −141 74 457 Q NE2 547 285 −160 78 458 E N 515 327 −131 52 458 E CA 502 332 −135 52 458 E C 501 347 −135 56 458 E O 511 354 −134 58 458 E CB 491 326 −127 54 458 E CG 495 320 −113 64 458 E CD 483 315 −106 67 458 E OE1 480 303 −109 56 458 E OE2 477 322 −98 69

TABLE 5c Crystal coordinates for crystalline complex of PXR-LBD-L10-SRC and SR12813 (crystal 3). The following table contains one line for each atom of SR12813 in both of the two observed PXR-LBD-L10-SRC monomers complexed with SR12813 in the orthorhombic asymmetric unit. The columns are: 1) residue number, 2) the letter X, 3) atom name, 4) x-coordinate multiplied by 10, 5) y-coordinate multiplied by 10, 6) z-coordinate multiplied by 10, and 7) B-factor 1 X C1 125 338 264 70 1 X C2 138 334 266 72 1 X C3 145 322 262 71 1 X C4 136 313 254 70 1 X C5 123 316 252 71 1 X C6 117 328 257 68 1 X C7 114 307 244 75 1 X C8 106 312 235 76 1 X P9 97 299 225 76 1 X P10 103 329 230 80 1 X O11 146 342 273 74 1 X C12 118 351 269 69 1 X C13 160 317 263 72 1 X C14 120 353 284 66 1 X C15 103 352 265 66 1 X C16 125 364 263 69 1 X C17 161 303 256 74 1 X C18 171 326 257 76 1 X C19 163 316 279 74 1 X O20 100 286 231 80 1 X O21 104 300 211 74 1 X C22 118 299 211 72 1 X C23 122 300 196 69 1 X O24 81 301 226 78 1 X C25 73 292 218 77 1 X C26 59 297 221 73 1 X O27 96 338 239 79 1 X O28 118 335 227 77 1 X C29 117 349 222 74 1 X C30 131 354 220 75 1 X O31 96 330 215 86 1 X C32 84 336 216 87 1 X C33 78 337 203 86 2 X C1 515 398 146 77 2 X C2 501 400 144 77 2 X C3 492 394 134 74 2 X C4 499 385 125 73 2 X C5 513 382 127 75 2 X C6 520 389 137 75 2 X C7 519 373 118 79 2 X C8 527 363 123 85 2 X P9 534 350 112 86 2 X P10 532 361 141 91 2 X O11 495 408 153 82 2 X C12 524 404 157 77 2 X C13 477 396 131 72 2 X C14 523 420 156 75 2 X C15 538 399 156 75 2 X C16 519 401 172 76 2 X C17 473 387 118 74 2 X C18 467 392 142 77 2 X C19 474 411 126 64 2 X O20 530 354 98 85 2 X O21 526 337 115 88 2 X C22 512 338 117 84 2 X C23 506 324 120 80 2 X O24 549 349 111 87 2 X C25 554 338 102 87 2 X C26 569 338 103 86 2 X O27 540 371 147 91 2 X O28 518 359 149 90 2 X C29 521 358 164 90 2 X C30 508 356 172 90 2 X O31 538 346 143 89 2 X C32 551 345 138 88 2 X C33 555 331 141 87

TABLE 5d Crystal coordinates for crystalline complex of PXR-LBD-L10-SRC and SR12813 (crystal 3). The following table contains one line for each solvent atom in both of the two observed PXR-LBD-L10-SRC monomers complexed with SR12813 in the orthorhombic asymmetric unit. The columns are: 1) residue number, 2) the letter O, 3) atom name, 4) x-coordinate multiplied by 10, 5) y-coordinate multiplied by 10, 6) z-coordinate multiplied by 10, and 7) B-factor 1 O OW0 540 553 104 24 2 O OW0 119 321 430 28 3 O OW0 513 522 12 35 4 O OW0 549 258 −162 35 5 O OW0 188 167 368 33 6 O OW0 657 625 58 37 7 O OW0 135 212 302 38 8 O OW0 643 399 −4 37 9 O OW0 −18 221 304 39 10 O OW0 5 311 517 42 11 O OW0 162 198 302 39 12 O OW0 149 243 472 39 13 O OW0 −42 348 436 48 14 O OW0 493 416 17 44 15 O OW0 148 398 411 44 16 O OW0 424 292 146 41 17 O OW0 487 276 10 45 18 O OW0 110 138 250 43 19 O OW0 210 314 153 45 20 O OW0 133 109 429 47 21 O OW0 663 626 33 47 22 O OW0 −8 378 595 47 23 O OW0 647 644 69 44 24 O OW0 547 302 −180 48 25 O OW0 −6 287 342 50 26 O OW0 621 460 177 46 27 O OW0 191 364 414 55 28 O OW0 575 251 −157 45 29 O OW0 408 334 18 53 30 O OW0 5 394 278 53 31 O OW0 191 147 328 50 32 O OW0 126 225 409 36 33 O OW0 164 270 428 47 34 O OW0 153 304 409 37 35 O OW0 187 234 449 50 36 O OW0 343 322 88 72 37 O OW0 141 230 494 50 38 O OW0 498 589 30 50 39 O OW0 487 551 59 51 40 O OW0 510 567 89 56 41 O OW0 502 537 95 52 42 O OW0 465 418 14 51 43 O OW0 685 477 46 62 44 O OW0 721 350 −22 105

The present invention is not to be limited in scope by the specific embodiments described herein. Indeed, various modifications of the invention in addition to those described herein will become apparent to those skilled in the art from the foregoing description. Such modifications are intended to fall within the scope of the appended claims.

Patents, patent applications, publications, product descriptions, and protocols are cited throughout this application, the disclosures of which are incorporated herein by reference in their entireties for all purposes. 

1.-12. (canceled)
 13. A crystalline composition comprising (a) a PXR-LBD-L10-SRC1 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 24 which is in space group P2₁2₁2₁ and comprises unit cell dimensions a=84.2 Å, b=90.0 Å, c=106.6 Å, α=β=γ=90°; (b) a PXR-LBD-L10-SRC1 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 24 which is in space group P4₃2₁2 and comprises unit cell dimensions a=b=94.2 Å, c=88.2 Å, α=β=γ=90°; or (c) a PXR-LBD-L10-SRC1 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 24 complexed with

which is in space group P2₁2₁2₁ and comprises unit cell dimensions a=86.0 Å, b=89.3 Å, c=106.0 Å, α=β=γ=90°.
 14. The crystalline composition of claim 13 which comprises a first monomer characterized by the structural coordinates set forth in Table 3a and a second monomer characterized by the structural coordinates set forth in Table 3b.
 15. The crystalline composition of claim 13 which is characterized by the structural coordinates of table 4a.
 16. The crystalline composition of claim 13 comprising a first monomer characterized by the structural coordinates set forth in Table 5a, a second monomer characterized by the structural coordinates set forth in Table 5b; and SR12813 complexed with said polypeptides characterized by the structural coordinates set forth in Table 5c.
 17. The crystalline composition of claim 13 wherein crystal (a) diffracts X-rays to a resolution of 2.3 Å.
 18. The crystalline composition of claim 13 wherein crystal (b) diffracts X-rays to a resolution of 2.2 Å.
 19. The crystalline composition of claim 13 wherein crystal (c) diffracts X-rays to a resolution of 2.2 Å. 20.-27. (canceled) 